Th22 cell

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Th22 cells (T helper cells type 22) are subpopulation of CD4+ T cells that produce interleukin-22 (IL-22). They play a role in the protective mechanisms against variety of bacterial pathogens, tissue repair and wound healing, and also in pathologic processes, including inflammations, autoimmunity, tumors, and digestive organs damages. [1]

Contents

Characterization

Th22 cells are mainly defined by their high secretion of interleukin-22 (IL-22). [2] Besides IL-22, Th22 cells also produce other cytokines, such as interleukin-13 (IL-13) and tumor necrosis factor alpha (TNF-alpha), but in very small quantities. [3] Additionally, they could be characterized by their cell surface expression of CD3, CD4, CD28, number of chemokine receptors CCR10, CCR6, CCR4 that are associated with cutaneous T cell homing, and platelet-derived growth factor receptor (PGDFR). [1]

Differentiation

Th22 cells differentiate from naive T-lymphocytes in presence of number of cytokines and transcription factors.

Cytokines in differentiation

Activated naive CD4+ T cells differentiate into Th22 cells under the influence of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). This process can be inhibited by the addition of increasing concentrations of transforming growth factor beta (TGF-beta). [4] The combination of interleukin-21 (IL-21) and interleukin-23 (IL-23) can also induce the differentiation of naive T cells into Th22 cells via the endogenous toll-like receptor 4 ligand (TLR4), stimulating keratinocytes to secrete interleukin-23 (IL-23) and binds to the IL-23 receptor of skin dendritic cells. This mechanism induces the differentiation into Th22 cells and secretion of interleukin-22 (IL−22). [5]

Transcription factors in differentiation

Downstream signaling of the transcription factor aryl hydrocarbon receptor (AHR) is essential for Th22 production of interleukin-22 (IL-22). RORγt acts as a positive transcription factor and T-bet acts as a negative transcription factor for Th22 cell differentiation. [2] However, additional intracellular molecules involved in Th22 differentiation are still being investigated. [6]

Physiological functions

Through their production of interleukin-22 (IL-22), Th22 cells have been shown to be protective against a number of bacterial and viral pathogens. Interleukin-22 (IL-22) regulates different innate immune mechanisms to eliminate infiltration of invasive pathogens into the skin, gut and respiratory tract. Interleukin-22 (IL-22) influences keratinocytes and epithelial cells to stimulate proliferation and differentiation, thus promoting wound healing and cohesion of barrier integrity. Interleukin-22 (IL-22) also enhances stromal secretion of antimicrobial peptides, as well as production of the chemokines which promote recruitment of other immune cells. [7]

Th22 in diseases

Th22 has both pathologic and protective claimed roles when maintaining immunologic homeostasis. However, the role of Th22 in pathological processes has not been completely identified.

AIDS

It seems that Th22 cells could play a protective role in patients with AIDS. CCR5 and α4β7 molecules expressed by Th22 cells were able to bind to the circulating HIV receptor, and thus via interleukin-22 (IL-22) production protect against intestinal epithelial damage, leading to a mechanism of resistance against HIV-induced destruction of epithelial cell integrity. [4]

Psoriasis

In psoriasis Th22 cells have been causally linked to pathological processes. In patients with psoriasis the levels of Th22 cells and interleukin-22 (IL-22) were increased. High levels of interleukin-22 (IL-22) together with interleukin-6 (IL-6) can induce the expression of antimicrobial proteins (AMPs), and stimulate the keratinocytes to secrete proinflammatory mediators and chemokines in the skin. In addition, it can also inhibit keratinocyte differentiation and inhibit the normal skin healing process. [8]

Systemic lupus erythematosus

The role of Th22 cells in systematic lupus erythematous (SLE) is still unclear. In some patients levels of Th22 cells and interleukin-22 (IL-22) were increased, which correlated with disease activity, but decreased levels of interleukin-22 (IL-22) and Th22 cells were also reported. Interleukin-22 (IL-22) is a cytokine involved in recruiting neutrophils in response to microbe invading, and in the case of lupus, it seems that interleukin 22 (IL-22) is involved in inflammatory and pathological processes via recruiting of immune cells. On the other hand, Th22 cells might be a better predictor of systematic lupus erythematous (SLE) development than Th17 cells. [9]

Tumors

Th22 cells are involved in tumorigenesis in cases of hepatocellular carcinoma, liposarcoma or colon cancer, and affect tumor tissue in two different pathways. Overexpression of interleukin-22 (IL-22) or Th22 cells may result in the progression of cancer growth and cause malignant epithelial cell proliferation. However, physiological functions of Th22 cells are tissue repair and wound healing. Some studies have shown a possible anti-tumor effect of these cells, and normal interleukin-22 (IL-22) secretion leads to tissue repair. [10]

Related Research Articles

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<span class="mw-page-title-main">Cell-mediated immunity</span> Immune response that does not involve antibodies

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<span class="mw-page-title-main">Interleukin 8</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">Interleukin 1-alpha</span> Protein-coding gene in the species Homo sapiens

Interleukin-1 alpha also known as hematopoietin 1 is a cytokine of the interleukin 1 family that in humans is encoded by the IL1A gene. In general, Interleukin 1 is responsible for the production of inflammation, as well as the promotion of fever and sepsis. IL-1α inhibitors are being developed to interrupt those processes and treat diseases.

<span class="mw-page-title-main">Interleukin 1 beta</span> Mammalian protein found in Homo sapiens

Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the IL1B gene. There are two genes for interleukin-1 (IL-1): IL-1 alpha and IL-1 beta. IL-1β precursor is cleaved by cytosolic caspase 1 to form mature IL-1β.

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

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<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 24</span> Protein-coding gene in the species Homo sapiens

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

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

<span class="mw-page-title-main">Interleukin 20</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Interleukin 17</span> Group of proteins

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<span class="mw-page-title-main">CXCL1</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">IL17A</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Interleukin 23</span> Heterodimeric cytokine acting as mediator of inflammation

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<span class="mw-page-title-main">Type 3 innate lymphoid cells</span>

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T helper cell 22, also known as the Th22 cell, are a type of immune cell. Th22 are a derivative of naïve CD4+ T cells induced by the ligand activation of the transcription factor aryl hydrocarbon receptor (AhR), which uses environmental, metabolic, microbial, and dietary cues to control complex transcriptional programmes. Th22 cell’s function is mediated by its ligand specific cytokine interleukin-22 (IL-22).

References

  1. 1 2 Tamasauskiene, Laura; Sitkauskiene, Brigita (August 2018). "Role of Th22 and IL-22 in pathogenesis of allergic airway diseases: Pro-inflammatory or anti-inflammatory effect?". Pediatrics & Neonatology. 59 (4): 339–344. doi: 10.1016/j.pedneo.2017.11.020 . PMID   29292068. S2CID   21187991.
  2. 1 2 Cui, Guanglin (2019-10-04). "TH9, TH17, and TH22 Cell Subsets and Their Main Cytokine Products in the Pathogenesis of Colorectal Cancer". Frontiers in Oncology. 9: 1002. doi: 10.3389/fonc.2019.01002 . ISSN   2234-943X. PMC   6787935 . PMID   31637216.
  3. ↑ Jiang, Qi; Yang, Guocan; Xiao, Fan; Xie, Jue; Wang, Shengjun; Lu, Liwei; Cui, Dawei (2021-07-06). "Role of Th22 Cells in the Pathogenesis of Autoimmune Diseases". Frontiers in Immunology. 12: 688066. doi: 10.3389/fimmu.2021.688066 . ISSN   1664-3224. PMC   8290841 . PMID   34295334.
  4. 1 2 Gong, Jianguang; Zhan, Huifang; Liang, Yan; He, Qiang; Cui, Dawei (2021-08-09). "Role of Th22 Cells in Human Viral Diseases". Frontiers in Medicine. 8: 708140. doi: 10.3389/fmed.2021.708140 . ISSN   2296-858X. PMC   8381044 . PMID   34434945.
  5. ↑ Yeste, Ada; Mascanfroni, Ivan D.; Nadeau, Meghan; Burns, Evan J.; Tukpah, Ann-Marcia; Santiago, Andrezza; Wu, Chuan; Patel, Bonny; Kumar, Deepak; Quintana, Francisco J (September 2014). "IL-21 induces IL-22 production in CD4+ T cells". Nature Communications. 5 (1): 3753. Bibcode:2014NatCo...5.3753Y. doi:10.1038/ncomms4753. ISSN   2041-1723. PMC   4157605 . PMID   24796415.
  6. ↑ de Araújo, Eliseu Frank; Preite, Nycolas Willian; Veldhoen, Marc; Loures, Flávio Vieira; Calich, Vera Lúcia Garcia (December 2020). "Pulmonary paracoccidioidomycosis in AhR deficient hosts is severe and associated with defective Treg and Th22 responses". Scientific Reports. 10 (1): 11312. doi:10.1038/s41598-020-68322-6. ISSN   2045-2322. PMC   7347857 . PMID   32647342.
  7. ↑ T helper cell differentiation and their function. Bing Sun. Dordrecht. 2014. ISBN   978-94-017-9487-9. OCLC   892842111.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  8. ↑ Nguyen, T.; Lestienne, F.; Cousy, A.; Mengeaud, V.; Castex‐Rizzi, N. (August 2020). "Effective inhibition of Th17/Th22 pathway in 2D and 3D human models of psoriasis by Celastrol enriched plant cell culture extract". Journal of the European Academy of Dermatology and Venereology. 34 (S6): 3–9. doi: 10.1111/jdv.16475 . ISSN   0926-9959. PMID   32783265. S2CID   221108530.
  9. ↑ Yang, Ji; Yang, Xue; Wang, Luman; Li, Ming (March 2020). "B cells control lupus autoimmunity by inhibiting Th17 and promoting Th22 cells". Cell Death & Disease. 11 (3): 164. doi:10.1038/s41419-020-2362-y. ISSN   2041-4889. PMC   7054432 . PMID   32127533.
  10. ↑ Doulabi, Hassan; Masoumi, Elham; Rastin, Maryam; Foolady Azarnaminy, Afsaneh; Esmaeili, Seyed-Alireza; Mahmoudi, Mahmoud (January 2022). "The role of Th22 cells, from tissue repair to cancer progression". Cytokine. 149: 155749. doi:10.1016/j.cyto.2021.155749. PMID   34739898. S2CID   243483226.
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