Interleukin 10

Last updated

IL10
IL10 Crystal Structure.rsh.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases IL10 , CSIF, GVHDS, IL-10, IL10A, TGIF, interleukin 10
External IDs OMIM: 124092; MGI: 96537; HomoloGene: 478; GeneCards: IL10; OMA:IL10 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

3586

16153

Ensembl

ENSG00000136634

ENSMUSG00000016529

UniProt

P22301

P18893

RefSeq (mRNA)

NM_000572

NM_010548

RefSeq (protein)

NP_000563

NP_034678

Location (UCSC) Chr 1: 206.77 – 206.77 Mb Chr 1: 130.95 – 130.95 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans, interleukin 10 is encoded by the IL10 gene. [5] IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins. [6] Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and Tyk2 respectively. [6]

Contents

Gene and protein structure

The IL-10 protein is a homodimer; each of its subunits is 178-amino-acid long. [7]

IL-10 is classified as a class-2 cytokine, a set of cytokines including IL-19, IL-20, IL-22, IL-24 (Mda-7), IL-26 and interferons type-I (IFN-alpha, -beta, -epsilon, -kappa, -omega), type-II (IFN-gamma) and type-III (IFN-lambda, [8] including IL-28A, IL-28B, IL-29, and IFNL4). [9]

Expression and synthesis

In humans, IL-10 is encoded by the IL10 gene, which is located on chromosome 1 and comprises five exons, [5] and is primarily produced by monocytes and, to a lesser extent, lymphocytes, namely type-II T helper cells (TH2), mast cells, CD4 + CD25 +Foxp3+ regulatory T cells, and in a certain subset of activated T cells and B cells. IL-10 can be produced by monocytes upon PD-1 triggering in these cells. [10] IL-10 upregulation is also mediated by GPCRs, such as beta-2 adrenergic [11] and type 2 cannabinoid [12] receptors. The expression of IL-10 is minimal in unstimulated tissues and seems to require triggering by commensal or pathogenic flora. [13] IL-10 expression is tightly regulated at the transcriptional and post-transcriptional level. Extensive IL-10 locus remodeling is observed in monocytes upon stimulation of TLR or Fc receptor pathways. [14] IL-10 induction involves ERK1/2, p38 and NF-κB signalling and transcriptional activation via promoter binding of the transcription factors NF-κB and AP-1. [14] IL-10 may autoregulate its expression via a negative feed-back loop involving autocrine stimulation of the IL-10 receptor and inhibition of the p38 signaling pathway. [15] Additionally, IL-10 expression is extensively regulated at the post-transcriptional level, which may involve control of mRNA stability via AU-rich elements [16] and by microRNAs such as let-7 [17] or miR-106. [18]

Function

IL-10 is a cytokine with multiple, pleiotropic, effects in immunoregulation and inflammation. It downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. IL-10 can block NF-κB activity, and is involved in the regulation of the JAK-STAT signaling pathway.

Discovered in 1991, [19] IL-10 was initially reported to suppress cytokine secretion, antigen presentation and CD4+ T cell activation. [20] [21] [22] [23] Further investigation has shown that IL-10 predominantly inhibits lipopolysaccharide (LPS) and bacterial product mediated induction of the pro-inflammatory cytokines TNFα, [24] IL-1β, [24] IL-12, [25] and IFNγ [26] secretion from Toll-Like Receptor (TLR) triggered myeloid lineage cells.

Effect on tumors

Over time a more nuanced picture of IL-10's function has emerged as treatment of tumor bearing mice has been shown to inhibit tumor metastasis. [27] Additional investigation by multiple laboratories has generated data that further supports IL-10's immunostimulatory capacity in an immunoncology context. Expression of IL-10 from transfected tumor cell lines [28] [29] in IL-10 transgenic mice [30] or dosing with IL-10 leads to control of primary tumor growth and decreased metastatic burden. [31] [32] More recently, PEGylated recombinant murine IL-10 (PEG-rMuIL-10) has been shown to induce IFNγ and CD8+ T cell dependent anti-tumor immunity. [33] [34] More specifically, PEGylated recombinant human IL-10 (PEG-rHuIL-10) has been shown to enhance CD8+ T cell secretion of the cytotoxic molecules Granzyme B and Perforin and potentiate T cell receptor dependent IFNγ secretion. [35]

Role in disease

A study in mice has shown that IL-10 is also produced by mast cells, counteracting the inflammatory effect that these cells have at the site of an allergic reaction. [36]

IL-10 is capable of inhibiting synthesis of pro-inflammatory cytokines such as IFN-γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as macrophages and Th1 T cells. It also displays a potent ability to suppress the antigen-presentation capacity of antigen presenting cells; however, it is also stimulatory towards certain T cells (Th2) and mast cells and stimulates B cell maturation and antibody production.

IL-10 checks the inducible form of Cyclo-oxygenase, Cyclo-oxygenase-2 (COX-2). Lack of IL-10 has been shown to cause COX activation and resultant Thromboxane receptor activation to cause vascular endothelial and cardiac dysfunctions in mice. Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age. [37]

IL-10 is linked to the myokines, as exercise provokes an increase in circulating levels of IL-1ra, IL-10, and sTNF-R, suggesting that physical exercise fosters an environment of anti-inflammatory cytokines. [38] [39]

Lower levels of IL-10 have been observed in individuals diagnosed with multiple sclerosis when compared to healthy individuals. [40] Due to a decrease in IL-10 levels, TNFα levels are not regulated effectively as IL-10 regulates the TNF-α-converting enzyme. [41] As a result, TNFα levels rise and result in inflammation. [42] TNFα itself induces demyelination of the oligodendroglial via TNF receptor 1, while chronic inflammation has been linked to demyelination of neurons. [42]

In melanoma cell lines, IL-10 modulates the surface expression of NKG2D ligands. [43]

In addition, Forkhead box protein 3 (Foxp3) as a transcription factor is an essential molecular marker of regulatory T (Treg) cells. Foxp3 polymorphism (rs3761548) might be involved in cancer progression like gastric cancer through influencing Tregs function and the secretion of immunomodulatory cytokines such as IL-10, IL-35, and TGF-β. [44]

A recent mouse study indicates that IL-10 regulates CD36, a key phagocytosis effector, promoting hematoma clearance after intracerebral hemorrhage. [45] IL-10 deficiency aggravates traumatic brain injury in male but not female mice. [46]

Clinical use or trials

Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. [47] and, indeed, patients with Crohn's disease react favorably towards treatment with recombinant interleukin-10-producing bacteria, demonstrating the importance of IL-10 for counteracting the hyperactive immune response in the human body. [48]

Due to the data, thousands of patients with a variety of autoimmune diseases were treated with recombinant human IL-10 (rHuIL-10) in clinical trials. Contrary to expectations, rHuIL-10 treatment did not significantly impact disease in patients with Crohn's disease [49] [50] [51] or rheumatoid arthritis. [52] rHuIL-10 treatment initially exhibited promising clinical data in psoriasis, [53] but failed to achieve clinical significance in a randomized, double blind, placebo controlled Phase II trial. [54] Further investigation of rHuIL-10's effects in humans suggests that rather than inhibiting inflammation, rHuIL-10 is capable of exerting pro-inflammatory effects. [55] [56]

PEGylated forms

Further to these data, a Phase I immunoncology clinical trial is currently being conducted to assess the therapeutic capacity of PEGylated recombinant human IL-10 (PEG-rHuIL-10, AM0010). [57] Consistent with preclinical immunoncology data, investigators report substantial anti-tumor efficacy. [57] Contrary to the reported immunosuppressive effects of IL-10 generated in vitro and in vivo, [21] [22] [23] [24] [25] treatment of cancer patients with PEG-rHuIL-10 elicits a dose titratable induction of the immune stimulatory cytokines IFNγ, IL-18, IL-7, GM-CSF and IL-4. [57] Furthermore, treated patients exhibit fold increases of peripheral CD8+ T cells expressing markers of activation, such as programmed death 1 (PD1)+, lymphocyte activation gene 3 (LAG3)+ and increased Fas Ligand (FasL) and a decrease in serum TGFβ. [57] These findings are consistent with the published preclinical immunoncology reports using PEG-rMuIL-10 [33] [34] and with previous findings treating humans with rHuIL-10. [55] [56] These data suggest that while IL-10 can exert immunosuppressive effects in context of bacterial product stimulated myeloid cells, rHuIL-10/PEG-rHuIL-10 treatment of humans is predominantly immunostimulatory. As of 2018 AM0010 (aka pegilodecakin) is in phase 3 clinical trials. [58]

Interactions

IL-10 has been shown to interact with Interleukin 10 receptor, alpha subunit. [59] [60] [61] [62] [63]

The receptor complex for IL-10 also requires the IL10R2 chain to initiate signalling. This ligand–receptor combination is found in birds and frogs, and is also likely to exist in bony fish.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Cytokine</span> Broad and loose category of small proteins important in cell signaling

Cytokines are a broad and loose category of small proteins important in cell signaling. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptors on the target cell surface. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.

Interleukins (ILs) are a group of cytokines that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related proteins.

<span class="mw-page-title-main">Interleukin 12</span> Interleukin

Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, helper T cells and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects.

<span class="mw-page-title-main">Interleukin 4</span> Mammalian protein found in Mus musculus

The interleukin 4 is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 is produced primarily by mast cells, Th2 cells, eosinophils and basophils. It is closely related and has functions similar to IL-13.

<span class="mw-page-title-main">Interferon gamma</span> InterPro Family

Interferon gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed interferon gamma release assay used to test for tuberculosis. In humans, the IFNG protein is encoded by the IFNG gene.

<span class="mw-page-title-main">Interleukin 23 subunit alpha</span>

Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene. The protein is also known as IL-23p19. It is one of the two subunits of the cytokine Interleukin-23.

<span class="mw-page-title-main">Interleukin 15</span> Cytokine with structural similarity to Interleukin-2

Interleukin-15 (IL-15) is a protein that in humans is encoded by the IL15 gene. IL-15 is an inflammatory cytokine with structural similarity to Interleukin-2 (IL-2). Like IL-2, IL-15 binds to and signals through a complex composed of IL-2/IL-15 receptor beta chain (CD122) and the common gamma chain. IL-15 is secreted by mononuclear phagocytes following infection by virus(es). This cytokine induces the proliferation of natural killer cells, i.e. cells of the innate immune system whose principal role is to kill virally infected cells.

<span class="mw-page-title-main">Interleukin 33</span> IL-33 induces helper T cells, mast cells, eosinophils and basophils to produce type 2 cytokines.

Interleukin 33 (IL-33) is a protein that in humans is encoded by the IL33 gene.

<span class="mw-page-title-main">Interleukin 30</span> Protein-coding gene in the species Homo sapiens

Interleukin 30 (IL-30) forms one chain of the heterodimeric cytokine called interleukin 27 (IL-27), thus it is also called IL27-p28. IL-27 is composed of α chain p28 and β chain Epstain-Barr induce gene-3 (EBI3). The p28 subunit, or IL-30, has an important role as a part of IL-27, but it can be secreted as a separate monomer and has its own functions in the absence of EBI3. The discovery of IL-30 as individual cytokine is relatively new and thus its role in the modulation of the immune response is not fully understood.

<span class="mw-page-title-main">Interleukin 29</span> Protein-coding gene in the species Homo sapiens

Interleukin-29 (IL-29) is a cytokine and it belongs to type III interferons group, also termed interferons λ (IFN-λ). IL-29 plays an important role in the immune response against pathogenes and especially against viruses by mechanisms similar to type I interferons, but targeting primarily cells of epithelial origin and hepatocytes.

<span class="mw-page-title-main">Interleukin 26</span>

Interleukin-26 (IL-26) is a protein that in humans is encoded by the IL26 gene.

<span class="mw-page-title-main">Interleukin 22</span> Protein, encoded in humans by IL22 gene

Interleukin-22 (IL-22) is a protein that in humans is encoded by the IL22 gene.

<span class="mw-page-title-main">Interleukin 19</span> Protein-coding gene in the species Homo sapiens

Interleukin 19 (IL-19) is an immunosuppressive protein that belongs to the IL-10 cytokine subfamily.

<span class="mw-page-title-main">Interleukin-1 receptor antagonist</span> Protein and coding gene in humans

The interleukin-1 receptor antagonist (IL-1RA) is a protein that in humans is encoded by the IL1RN gene.

<span class="mw-page-title-main">Tyrosine kinase 2</span> Enzyme and coding gene in humans

Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the TYK2 gene.

Interleukin 35 (IL-35) is a recently discovered anti-inflammatory cytokine from the IL-12 family. Member of IL-12 family - IL-35 is produced by wide range of regulatory lymphocytes and plays a role in immune suppression. IL-35 can block the development of Th1 and Th17 cells by limiting early T cell proliferation.

Interleukin-28 receptor is a type II cytokine receptor found largely in epithelial cells. It binds type 3 interferons, interleukin-28 A, Interleukin-28B, interleukin 29 and interferon lambda 4. It consists of an α chain and shares a common β subunit with the interleukin-10 receptor. Binding to the interleukin-28 receptor, which is restricted to select cell types, is important for fighting infection. Binding of the type 3 interferons to the receptor results in activation of the JAK/STAT signaling pathway.

<span class="mw-page-title-main">Interleukin-17A</span> Protein-coding gene in the species Homo sapiens

Interleukin-17A is a protein that in humans is encoded by the IL17A gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene.

<span class="mw-page-title-main">Interleukin-1 family</span> Group of cytokines playing a key role in the regulation of immune and inflammatory responses

The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.

The IL-10 family is a family of interleukins.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000136634 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000016529 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Eskdale J, Kube D, Tesch H, Gallagher G (1997). "Mapping of the human IL10 gene and further characterization of the 5' flanking sequence". Immunogenetics. 46 (2): 120–128. doi:10.1007/s002510050250. PMID   9162098. S2CID   30126106.
  6. 1 2 Mosser DM, Zhang X (December 2008). "Interleukin-10: new perspectives on an old cytokine". Immunological Reviews. 226 (1): 205–218. doi:10.1111/j.1600-065X.2008.00706.x. PMC   2724982 . PMID   19161426.
  7. ↑ Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J, Wlodawer A (June 1995). "Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma". Structure. 3 (6): 591–601. doi: 10.1016/S0969-2126(01)00193-9 . PMID   8590020.
  8. ↑ Lazear HM, Nice TJ, Diamond MS (July 2015). "Interferon-λ: Immune Functions at Barrier Surfaces and Beyond". Immunity. 43 (1): 15–28. doi:10.1016/j.immuni.2015.07.001. PMC   4527169 . PMID   26200010.
  9. ↑ Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB (2004). "Interleukin-10 and related cytokines and receptors". Annual Review of Immunology. 22 (1): 929–979. doi:10.1146/annurev.immunol.22.012703.104622. PMID   15032600.
  10. ↑ Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, et al. (April 2010). "Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection". Nature Medicine. 16 (4): 452–459. doi:10.1038/nm.2106. PMC   4229134 . PMID   20208540.
  11. ↑ Ağaç D, Estrada LD, Maples R, Hooper LV, Farrar JD (November 2018). "The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion". Brain, Behavior, and Immunity. 74: 176–185. doi:10.1016/j.bbi.2018.09.004. PMC   6289674 . PMID   30195028.
  12. ↑ Saroz Y, Kho DT, Glass M, Graham ES, Grimsey NL (December 2019). "Cannabinoid Receptor 2 (CB2) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes". ACS Pharmacology & Translational Science. 2 (6): 414–428. doi: 10.1021/acsptsci.9b00049 . PMC   7088898 . PMID   32259074.
  13. ↑ Li X, Mai J, Virtue A, Yin Y, Gong R, Sha X, et al. (March 2012). "IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines". PLOS ONE. 7 (3): e33628. Bibcode:2012PLoSO...733628L. doi: 10.1371/journal.pone.0033628 . PMC   3306427 . PMID   22438968.
  14. 1 2 Saraiva M, O'Garra A (March 2010). "The regulation of IL-10 production by immune cells". Nature Reviews. Immunology. 10 (3): 170–181. doi:10.1038/nri2711. hdl: 1822/29592 . PMID   20154735. S2CID   6150977.
  15. ↑ Hammer M, Mages J, Dietrich H, Schmitz F, Striebel F, Murray PJ, et al. (October 2005). "Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10". European Journal of Immunology. 35 (10): 2991–3001. doi: 10.1002/eji.200526192 . PMID   16184516.
  16. ↑ Powell MJ, Thompson SA, Tone Y, Waldmann H, Tone M (July 2000). "Posttranscriptional regulation of IL-10 gene expression through sequences in the 3'-untranslated region". Journal of Immunology. 165 (1): 292–296. doi: 10.4049/jimmunol.165.1.292 . PMID   10861064.
  17. ↑ Schulte LN, Eulalio A, Mollenkopf HJ, Reinhardt R, Vogel J (May 2011). "Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family". The EMBO Journal. 30 (10): 1977–1989. doi:10.1038/emboj.2011.94. PMC   3098495 . PMID   21468030.
  18. ↑ Sharma A, Kumar M, Aich J, Hariharan M, Brahmachari SK, Agrawal A, et al. (April 2009). "Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a". Proceedings of the National Academy of Sciences of the United States of America. 106 (14): 5761–5766. Bibcode:2009PNAS..106.5761S. doi: 10.1073/pnas.0808743106 . PMC   2659714 . PMID   19307576.
  19. ↑ Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A (2001-01-01). "Interleukin-10 and the interleukin-10 receptor". Annual Review of Immunology. 19 (1): 683–765. doi:10.1146/annurev.immunol.19.1.683. PMID   11244051.
  20. ↑ de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE (November 1991). "Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes". The Journal of Experimental Medicine. 174 (5): 1209–1220. doi:10.1084/jem.174.5.1209. PMC   2119001 . PMID   1940799.
  21. 1 2 de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, et al. (October 1991). "Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression". The Journal of Experimental Medicine. 174 (4): 915–924. doi:10.1084/jem.174.4.915. PMC   2118975 . PMID   1655948.
  22. 1 2 Akdis CA, Joss A, Akdis M, Faith A, Blaser K (September 2000). "A molecular basis for T cell suppression by IL-10: CD28-associated IL-10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3-kinase binding". FASEB Journal. 14 (12): 1666–1668. doi: 10.1096/fj.99-0874fje . PMID   10973911. S2CID   40794643.
  23. 1 2 Joss A, Akdis M, Faith A, Blaser K, Akdis CA (June 2000). "IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway". European Journal of Immunology. 30 (6): 1683–1690. doi: 10.1002/1521-4141(200006)30:6<1683::AID-IMMU1683>3.0.CO;2-A . PMID   10898505.
  24. 1 2 3 Opp MR, Smith EM, Hughes TK (July 1995). "Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep". Journal of Neuroimmunology. 60 (1–2): 165–168. doi:10.1016/0165-5728(95)00066-b. PMID   7642744. S2CID   3786577.
  25. 1 2 Aste-Amezaga M, Ma X, Sartori A, Trinchieri G (June 1998). "Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10". Journal of Immunology. 160 (12): 5936–5944. doi:10.4049/jimmunol.160.12.5936. PMID   9637507. S2CID   15960096.
  26. ↑ Varma TK, Toliver-Kinsky TE, Lin CY, Koutrouvelis AP, Nichols JE, Sherwood ER (September 2001). "Cellular mechanisms that cause suppressed gamma interferon secretion in endotoxin-tolerant mice". Infection and Immunity. 69 (9): 5249–5263. doi:10.1128/iai.69.9.5249-5263.2001. PMC   98633 . PMID   11500393.
  27. ↑ Zheng LM, Ojcius DM, Garaud F, Roth C, Maxwell E, Li Z, et al. (August 1996). "Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism". The Journal of Experimental Medicine. 184 (2): 579–584. doi:10.1084/jem.184.2.579. PMC   2192723 . PMID   8760811.
  28. ↑ Sun H, Jackson MJ, Kundu N, Fulton AM (February 1999). "Interleukin-10 gene transfer activates interferon-gamma and the interferon-gamma-inducible genes Gbp-1/Mag-1 and Mig-1 in mammary tumors". International Journal of Cancer. 80 (4): 624–629. doi: 10.1002/(sici)1097-0215(19990209)80:4<624::aid-ijc23>3.0.co;2-9 . PMID   9935167.
  29. ↑ Sun H, Gutierrez P, Jackson MJ, Kundu N, Fulton AM (2000-04-01). "Essential role of nitric oxide and interferon-gamma for tumor immunotherapy with interleukin-10". Journal of Immunotherapy. 23 (2): 208–214. doi:10.1097/00002371-200003000-00005. PMID   10746547. S2CID   39224241.
  30. ↑ Groux H, Cottrez F, Rouleau M, Mauze S, Antonenko S, Hurst S, et al. (February 1999). "A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells". Journal of Immunology. 162 (3): 1723–1729. doi: 10.4049/jimmunol.162.3.1723 . PMID   9973435. S2CID   36990295.
  31. ↑ Fujii S, Shimizu K, Shimizu T, Lotze MT (October 2001). "Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ". Blood. 98 (7): 2143–2151. doi: 10.1182/blood.v98.7.2143 . PMID   11568001.
  32. ↑ Berman RM, Suzuki T, Tahara H, Robbins PD, Narula SK, Lotze MT (July 1996). "Systemic administration of cellular IL-10 induces an effective, specific, and long-lived immune response against established tumors in mice". Journal of Immunology. 157 (1): 231–238. doi:10.4049/jimmunol.157.1.231. PMID   8683120. S2CID   25596108.
  33. 1 2 Emmerich J, Mumm JB, Chan IH, LaFace D, Truong H, McClanahan T, et al. (July 2012). "IL-10 directly activates and expands tumor-resident CD8(+) T cells without de novo infiltration from secondary lymphoid organs". Cancer Research. 72 (14): 3570–3581. doi: 10.1158/0008-5472.CAN-12-0721 . PMID   22581824.
  34. 1 2 Mumm JB, Emmerich J, Zhang X, Chan I, Wu L, Mauze S, et al. (December 2011). "IL-10 elicits IFNγ-dependent tumor immune surveillance". Cancer Cell. 20 (6): 781–796. doi: 10.1016/j.ccr.2011.11.003 . PMID   22172723.
  35. ↑ Chan IH, Wu V, Bilardello M, Mar E, Oft M, Van Vlasselaer P, et al. (December 2015). "The Potentiation of IFN-γ and Induction of Cytotoxic Proteins by Pegylated IL-10 in Human CD8 T Cells". Journal of Interferon & Cytokine Research. 35 (12): 948–955. doi:10.1089/jir.2014.0221. PMID   26309093.
  36. ↑ Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ (October 2007). "Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B". Nature Immunology. 8 (10): 1095–1104. doi:10.1038/ni1503. PMID   17767162. S2CID   10972672.
  37. ↑ Sikka G, Miller KL, Steppan J, Pandey D, Jung SM, Fraser CD, et al. (February 2013). "Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age". Experimental Gerontology. 48 (2): 128–135. doi:10.1016/j.exger.2012.11.001. PMC   3744178 . PMID   23159957.
  38. ↑ Ostrowski K, Schjerling P, Pedersen BK (December 2000). "Physical activity and plasma interleukin-6 in humans--effect of intensity of exercise". European Journal of Applied Physiology. 83 (6): 512–515. doi:10.1007/s004210000312. PMID   11192058. S2CID   44759539.
  39. ↑ Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK (February 1999). "Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans". The Journal of Physiology. 515 (Pt 1): 287–291. doi:10.1111/j.1469-7793.1999.287ad.x. PMC   2269132 . PMID   9925898.
  40. ↑ Ozenci V, Kouwenhoven M, Huang YM, Xiao B, Kivisäkk P, Fredrikson S, et al. (May 1999). "Multiple sclerosis: levels of interleukin-10-secreting blood mononuclear cells are low in untreated patients but augmented during interferon-beta-1b treatment". Scandinavian Journal of Immunology. 49 (5): 554–561. doi: 10.1046/j.1365-3083.1999.00546.x . PMID   10320650.
  41. ↑ Brennan FM, Green P, Amjadi P, Robertshaw HJ, Alvarez-Iglesias M, Takata M (April 2008). "Interleukin-10 regulates TNF-alpha-converting enzyme (TACE/ADAM-17) involving a TIMP-3 dependent and independent mechanism". European Journal of Immunology. 38 (4): 1106–1117. doi: 10.1002/eji.200737821 . PMID   18383040.
  42. 1 2 Nakahara J, Maeda M, Aiso S, Suzuki N (February 2012). "Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy". Clinical Reviews in Allergy & Immunology. 42 (1): 26–34. doi:10.1007/s12016-011-8287-6. PMID   22189514. S2CID   21058811.
  43. ↑ Serrano AE, Menares-Castillo E, Garrido-Tapia M, Ribeiro CH, Hernández CJ, Mendoza-Naranjo A, et al. (March 2011). "Interleukin 10 decreases MICA expression on melanoma cell surface". Immunology and Cell Biology. 89 (3): 447–457. doi:10.1038/icb.2010.100. hdl: 10533/132162 . PMID   20714339. S2CID   205150174.
  44. ↑ Ezzeddini R, Somi MH, Taghikhani M, Moaddab SY, Masnadi Shirazi K, Shirmohammadi M, et al. (February 2021). "Association of Foxp3 rs3761548 polymorphism with cytokines concentration in gastric adenocarcinoma patients". Cytokine. 138: 155351. doi:10.1016/j.cyto.2020.155351. PMID   33127257. S2CID   226218796.
  45. ↑ Li Q, Lan X, Han X, Durham F, Wan J, Weiland A, et al. (May 2021). "Microglia-derived interleukin-10 accelerates post-intracerebral hemorrhage hematoma clearance by regulating CD36". Brain, Behavior, and Immunity. 94: 437–457. doi:10.1016/j.bbi.2021.02.001. PMC   8058329 . PMID   33588074.
  46. ↑ Gu Y, Dong Y, Wan J, Ren H, Koehler RC, Wang J (September 2022). "Interleukin-10 deficiency aggravates traumatic brain injury in male but not female mice". Experimental Neurology. 355: 114125. doi:10.1016/j.expneurol.2022.114125. PMID   35644427. S2CID   249070122.
  47. ↑ "Entrez Gene: IL10 interleukin 10".
  48. ↑ Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP, et al. (June 2006). "A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease". Clinical Gastroenterology and Hepatology. 4 (6): 754–759. doi:10.1016/j.cgh.2006.03.028. PMID   16716759.
  49. ↑ Fedorak RN, Gangl A, Elson CO, Rutgeerts P, Schreiber S, Wild G, et al. (December 2000). "Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group". Gastroenterology. 119 (6): 1473–1482. doi:10.1053/gast.2000.20229. PMID   11113068.
  50. ↑ Schreiber S, Fedorak RN, Nielsen OH, Wild G, Williams CN, Nikolaus S, et al. (December 2000). "Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group". Gastroenterology. 119 (6): 1461–1472. doi:10.1053/gast.2000.20196. PMID   11113067.
  51. ↑ van Deventer SJ, Elson CO, Fedorak RN (August 1997). "Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease. Crohn's Disease Study Group". Gastroenterology. 113 (2): 383–389. doi:10.1053/gast.1997.v113.pm9247454. PMID   9247454.
  52. ↑ van Roon J, Wijngaarden S, Lafeber FP, Damen C, van de Winkel J, Bijlsma JW (April 2003). "Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation". The Journal of Rheumatology. 30 (4): 648–651. PMID   12672180.
  53. ↑ Asadullah K, Döcke WD, Ebeling M, Friedrich M, Belbe G, Audring H, et al. (February 1999). "Interleukin 10 treatment of psoriasis: clinical results of a phase 2 trial". Archives of Dermatology. 135 (2): 187–192. doi:10.1001/archderm.135.2.187. PMID   10052405.
  54. ↑ Kimball AB, Kawamura T, Tejura K, Boss C, Hancox AR, Vogel JC, et al. (October 2002). "Clinical and immunologic assessment of patients with psoriasis in a randomized, double-blind, placebo-controlled trial using recombinant human interleukin 10". Archives of Dermatology. 138 (10): 1341–1346. doi: 10.1001/archderm.138.10.1341 . PMID   12374540.
  55. 1 2 Lauw FN, Pajkrt D, Hack CE, Kurimoto M, van Deventer SJ, van der Poll T (September 2000). "Proinflammatory effects of IL-10 during human endotoxemia". Journal of Immunology. 165 (5): 2783–2789. doi: 10.4049/jimmunol.165.5.2783 . PMID   10946310.
  56. 1 2 Tilg H, van Montfrans C, van den Ende A, Kaser A, van Deventer SJ, Schreiber S, et al. (February 2002). "Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma". Gut. 50 (2): 191–195. doi:10.1136/gut.50.2.191. PMC   1773093 . PMID   11788558.
  57. 1 2 3 4 Infante JR, Naing A, Papadopoulos KP, Autio KA, Ott PA, Wong DJ, et al. (2015-05-20). "A first-in-human dose escalation study of PEGylated recombinant human IL-10 (AM0010) in advanced solid tumors". ASCO Meeting Abstracts. 33 (15_suppl): 3017. Archived from the original on 2015-12-22. Retrieved 2015-12-10.
  58. ↑ Early Data Supports Phase 3 Trial of Pegilodecakin as Possible Treatment for Advanced Pancreatic Cancer
  59. ↑ Ho AS, Liu Y, Khan TA, Hsu DH, Bazan JF, Moore KW (December 1993). "A receptor for interleukin 10 is related to interferon receptors". Proceedings of the National Academy of Sciences of the United States of America. 90 (23): 11267–11271. Bibcode:1993PNAS...9011267H. doi: 10.1073/pnas.90.23.11267 . PMC   47963 . PMID   8248239.
  60. ↑ Josephson K, Logsdon NJ, Walter MR (July 2001). "Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site". Immunity. 15 (1): 35–46. doi: 10.1016/S1074-7613(01)00169-8 . PMID   11485736.
  61. ↑ Tan JC, Braun S, Rong H, DiGiacomo R, Dolphin E, Baldwin S, et al. (May 1995). "Characterization of recombinant extracellular domain of human interleukin-10 receptor". The Journal of Biological Chemistry. 270 (21): 12906–12911. doi: 10.1074/jbc.270.21.12906 . PMID   7759550.
  62. ↑ Josephson K, McPherson DT, Walter MR (December 2001). "Purification, crystallization and preliminary X-ray diffraction of a complex between IL-10 and soluble IL-10R1". Acta Crystallographica. Section D, Biological Crystallography. 57 (Pt 12): 1908–1911. Bibcode:2001AcCrD..57.1908J. doi:10.1107/S0907444901016249. PMID   11717514.
  63. ↑ Hoover DM, Schalk-Hihi C, Chou CC, Menon S, Wlodawer A, Zdanov A (May 1999). "Purification of receptor complexes of interleukin-10 stoichiometry and the importance of deglycosylation in their crystallization". European Journal of Biochemistry. 262 (1): 134–141. doi: 10.1046/j.1432-1327.1999.00363.x . PMID   10231374.

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