Fumio Takei

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Fumio Takei is a Distinguished Scientist at the Provincial Health Services Authority and Terry Fox Laboratory, part of the British Columbia Cancer Agency. in Vancouver. He also is a Professor of Pathology and Laboratory Medicine at the University of British Columbia, Canada. [1] [2]

Contents

Education

In 1968, he received his bachelor's degree in biochemistry from the University of Tokyo, Japan. He continued his studies in immunology under the supervision of Dr. Julia Levy at the University of British Columbia(UBC) where he received his Ph.D. in 1976. His thesis was focused on “Specific Suppressor Cells in Mice Bearing a Syngeneic Mastocytoma” [3] Takei held a postdoctoral position in Microbiology at the University of British Columbia. He also trained in MRC Laboratory of Molecular Biology, Cambridge, England as a postdoctoral fellow with Drs. César Milstein and Ed Lennox before starting his own laboratory at the University of British Columbia.

Research and career

Takei has more than 30 years of experience in immunology, particularly innate lymphocytes. From 1990 to 2010, he mainly focused on the development and regulation of natural killer (NK) cell functions. In the beginning, he was more interested in T cells than NK cells. When his lab first cloned Ly-49, they found that it is a member of a large genetically related family rather than a T-cell receptor(TCR). [4] This happened before the first T cell receptor was cloned. Continuing this project was challenging at that time since the sequence of Ly-49 was not indicative of its function. However, after Wayne Yokoyama found that Ly-49 is MHC-I specific receptor on NK cells, [5] [6] Dr. Takei's lab continued working on other members of this family. They showed that each member of this family of highly polymorphic NK receptors, has distinct specificity for MHC I. [7] [8] [9] This is one of the biggest contributions to NK cell studies.

In 2010, while his lab was working on NK cells, they found an interesting similarity between natural helper (NH) cells and NK cells progenitors. They isolated natural helper (NH)-like cells from allergen-treated mouse lung and found the production of cytokines type 2, IL-5, and IL-13 in these population. [10] Identifying T cell-independent type 2 inflammation using an in vivo model of papain-induced lung resulted in finding a unique group of lymphocytes in mouse lungs, currently known as group 2 innate lymphoid cell (ILC2s). They showed that the production of Th-2 type cytokines in these populations involved in allergic inflammation. [11] Moreover, they proved that ILC2s play a major role in allergen-induced lung inflammation by developing ILC2 deficient mice. [8] More studies by his group showed other roles of ILC2s such as acquiring memory functions. [12] His lab is currently studying the regulation of ILC2s and their functional and developmental relationship with other lymphocytes as well as identifying other ILC populations induced by different allergens like ILC3s. They are also working on differences between tissue-resident versus migratory ILC2s.

Memberships

Selected publications

Related Research Articles

<span class="mw-page-title-main">Immune system</span> Biological system protecting an organism against disease

The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.

<span class="mw-page-title-main">Natural killer cell</span> Type of cytotoxic lymphocyte

Natural killer cells, also known as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. They are a kind of large granular lymphocytes (LGL), and belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, stressed cells, tumor cells, and other intracellular pathogens based on signals from several activating and inhibitory receptors. Most immune cells detect the antigen presented on major histocompatibility complex I (MHC-I) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class I. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.

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

Amphiregulin, also known as AREG, is a protein synthesized as a transmembrane glycoprotein with 252 aminoacids and it is encoded by the AREG gene. in humans.

Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specific antigen and contrasts the immune system's conventional role in eliminating foreign antigens. Depending on the site of induction, tolerance is categorized as either central tolerance, occurring in the thymus and bone marrow, or peripheral tolerance, taking place in other tissues and lymph nodes. Although the mechanisms establishing central and peripheral tolerance differ, their outcomes are analogous, ensuring immune system modulation.

<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">Intraepithelial lymphocyte</span>

Intraepithelial lymphocytes (IEL) are lymphocytes found in the epithelial layer of mammalian mucosal linings, such as the gastrointestinal (GI) tract and reproductive tract. However, unlike other T cells, IELs do not need priming. Upon encountering antigens, they immediately release cytokines and cause killing of infected target cells. In the GI tract, they are components of gut-associated lymphoid tissue (GALT).

Killer-cell immunoglobulin-like receptors (KIRs), are a family of type I transmembrane glycoproteins expressed on the plasma membrane of natural killer (NK) cells and a minority of T cells. In humans, they are encoded in the leukocyte receptor complex (LRC) on chromosome 19q13.4; the KIR region is approximately 150 kilobases and contains 14 loci, including 7 protein-coding genes and 2 pseudogenes.

<span class="mw-page-title-main">KLRD1</span>

CD94, also known as killer cell lectin-like receptor subfamily D, member 1 (KLRD1) is a human gene.

Ly49 is a family of membrane C-type lectin-like receptors expressed mainly on NK cells but also on other immune cells. Their primary role is to bind MHC-I molecules to distinguish between self healthy cells and infected or altered cells. Ly49 family is coded by Klra gene cluster and include genes for both inhibitory and activating paired receptors, but most of them are inhibitory. Inhibitory Ly49 receptors play a role in the recognition of self cells and thus maintain self-tolerance and prevent autoimmunity by suppressing NK cell activation. On the other hand, activating receptors recognise ligands from cancer or viral infected cells and are used when cells lack or have abnormal expression of MHC-I molecules, which activate cytokine production and cytotoxic activity of NK and immune cells.

NKG2 also known as CD159 is a receptor for natural killer cells. There are 7 NKG2 types: A, B, C, D, E, F and H. NKG2D is an activating receptor on the NK cell surface. NKG2A dimerizes with CD94 to make an inhibitory receptor (CD94/NKG2).

<span class="mw-page-title-main">CD69</span> Human lectin protein

CD69 is a human transmembrane C-Type lectin protein encoded by the CD69 gene. It is an early activation marker that is expressed in hematopoietic stem cells, T cells, and many other cell types in the immune system. It is also implicated in T cell differentiation as well as lymphocyte retention in lymphoid organs.

Gamma delta T cells are T cells that have a γδ T-cell receptor (TCR) on their surface. Most T cells are αβ T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, γδ T cells have a TCR that is made up of one γ (gamma) chain and one δ (delta) chain. This group of T cells is usually less common than αβ T cells. Their highest abundance is in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs).

<span class="mw-page-title-main">NCR3</span> Mammalian protein found in Homo sapiens

Natural cytotoxicity triggering receptor 3 is a protein that in humans is encoded by the NCR3 gene. NCR3 has also been designated as CD337 and as NKp30. NCR3 belongs to the family of NCR membrane receptors together with NCR1 (NKp46) and NCR2 (NKp44).

<span class="mw-page-title-main">KLRC2</span> Protein-coding gene in humans

NKG2-C type II integral membrane protein or NKG2C is a protein that in humans is encoded by the KLRC2 gene. It is also known as or cluster of differentiation 159c (CD159c).

<span class="mw-page-title-main">KLRG1</span> Protein-coding gene in humans

Killer cell lectin-like receptor subfamily G member 1 is a protein that in humans is encoded by the KLRG1 gene.

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid, and non- lymphoid tissues, and rarely in the blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis. Characteristics allowing their differentiation from other immune cells include the regular lymphoid morphology, absence of rearranged antigen receptors found on T cells and B cells, and phenotypic markers usually present on myeloid or dendritic cells.

Immunology is the study of the immune system during health and disease. Below is a list of immunology-related articles.

Cytokine-induced killer cells (CIK) cells are a group of immune effector cells featuring a mixed T- and natural killer (NK) cell-like phenotype. They are generated by ex vivo incubation of human peripheral blood mononuclear cells (PBMC) or cord blood mononuclear cells with interferon-gamma (IFN-γ), anti-CD3 antibody, recombinant human interleukin (IL)-1 and recombinant human interleukin (IL)-2.

<span class="mw-page-title-main">ILC2</span>

ILC2 cells, or type 2 innate lymphoid cells are a type of innate lymphoid cell. Not to be confused with the ILC. They are derived from common lymphoid progenitor and belong to the lymphoid lineage. These cells lack antigen specific B or T cell receptor because of the lack of recombination activating gene. ILC2s produce type 2 cytokines and are involved in responses to helminths, allergens, some viruses, such as influenza virus and cancer.

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

Type 3 innate lymphoid cells (ILC3) are immune cells from the lymphoid lineage that are part of the innate immune system. These cells participate in innate mechanisms on mucous membranes, contributing to tissue homeostasis, host-commensal mutualism and pathogen clearance. They are part of a heterogeneous group of innate lymphoid cells, which is traditionally divided into three subsets based on their expression of master transcription factors as well as secreted effector cytokines - ILC1, ILC2 and ILC3.

References

  1. ↑ "Fumio Takei | Terry Fox Laboratory". www.bccrc.ca. Retrieved 2022-08-02.
  2. ↑ "Fumio Takei". University of British Columbia Faculty of Medicine. Retrieved 2022-08-02.
  3. ↑ , Specific Suppressor Cells in Mice Bearing a Syngeneic Mastocytoma.
  4. ↑ , Wong, S., Freeman, J., Kelleher, C., Mager, D. and Takei, F., 2020. Ly-49 Multigene Family. New Members Of A Superfamily Of Type II Membrane Proteins With Lectin-Like Domains.
  5. ↑ , Smith, H, F Karlhofer, and W Yokoyama. "Ly-49 Multigene Family Expressed By IL-2-Activated NK Cells".
  6. ↑ Karlhofer, F., Orihuela, M. and Yokoyama, W., 1995. Ly-49-independent natural killer (NK) cell specificity revealed by NK cell clones derived from p53-deficient mice. The Journal of Experimental Medicine, 181(5), pp.1785-1795.
  7. ↑ Brennan, J., Mager, D., Jefferies, W. and Takei, F., 1994. Expression of different members of the Ly-49 gene family defines distinct natural killer cell subsets and cell adhesion properties. The Journal of Experimental Medicine, 180(6), pp.2287-2295.
  8. 1 2 Brennan, J., Mahon, G., Mager, D., Jefferies, W. and Takei, F., 1996. Recognition of class I major histocompatibility complex molecules by Ly-49: specificities and domain interactions. The Journal of Experimental Medicine, 183(4), pp.1553-1559.
  9. ↑ Takei, F., Brennan, J. and Mager, D., 1997. The Ly-49 family: genes, proteins and recognition of class I MHC. Immunological Reviews, 155(1), pp.67-77.
  10. ↑ Halim, T., Krauß, R., Sun, A. and Takei, F., 2012. Lung Natural Helper Cells Are a Critical Source of Th2 Cell-Type Cytokines in Protease Allergen-Induced Airway Inflammation. Immunity, 36(3), pp.451-463.
  11. ↑ Halim, T., Steer, C., Mathä, L., Gold, M., Martinez-Gonzalez, I., McNagny, K., McKenzie, A. and Takei, F., 2014. Group 2 Innate Lymphoid Cells Are Critical for the Initiation of Adaptive T Helper 2 Cell-Mediated Allergic Lung Inflammation. Immunity, 40(3), pp.425-435.
  12. ↑ Martinez-Gonzalez, I., Ghaedi, M., Steer, C., Mathä, L., Vivier, E. and Takei, F., 2018. ILC2 memory: Recollection of previous activation. Immunological Reviews, 283(1), pp.41-53.
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