Regulation of inflammation through JAK3-Stat6 pathway in dendritic cells

Kunihiro Yamaoka, Satoshi Kubo, Yoshiya Tanaka, Keisuke Maeshima

研究成果: Article

1 引用 (Scopus)

抄録

Dendritic cells (DCs) is the cell that act as source of the immune response by exquisitely presenting antigens to acquired immunity such as the T cells. Janus kinase (JAK) is a tyrosine kinase that is activated immediately after the cytokine binds to its unique receptor expressed on the cell surface. Among the JAKs, expression of JAK3 is limited on heamatopoietic cells and is indispensable for lymphocyte development and proliferation. We have demonstrated that JAK3-deficient DCs normally develop, uptake antigens, produce inflammatory cytokines and function as an antigen-presenting cell, although they over-produce IL-10. Among the transcription factors that are known to be activated by JAK3, we explored the phenotype of Stat6-deficient DCs which is a transcription factor specifically activated by JAK3. Interestingly, development, function and inflammatory cytokine production was normal with over-production of IL-10 which was in line with the JAK3Ideficient DCs. IL-4 is well known to activate JAK3-Stat6 in the cytoplasm and has been reported to be produced in the synovial fluid of rheumatoid arthritis patients. Hence the suppression of IL-10 production by IL-4 can be considered as one of the inflammatory process of arthritis. Moreover, induction of IL-10 production by DCs can be one mechanism of action of the JAK inhibitor (tofacitinib) which have shown high efficiency on active rheumatoid arthritis in clinical trials.

元の言語English
ページ(範囲)62-68
ページ数7
ジャーナルJapanese Journal of Clinical Immunology
35
発行部数1
DOI
出版物ステータスPublished - 2012
外部発表Yes

Fingerprint

Dendritic Cells
Interleukin-10
Inflammation
Janus Kinases
Cytokines
Interleukin-4
Rheumatoid Arthritis
Transcription Factors
Antigens
Synovial Fluid
Adaptive Immunity
Antigen-Presenting Cells
Protein-Tyrosine Kinases
Arthritis
Cytoplasm
Clinical Trials
Lymphocytes
T-Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

これを引用

Regulation of inflammation through JAK3-Stat6 pathway in dendritic cells. / Yamaoka, Kunihiro; Kubo, Satoshi; Tanaka, Yoshiya; Maeshima, Keisuke.

:: Japanese Journal of Clinical Immunology, 巻 35, 番号 1, 2012, p. 62-68.

研究成果: Article

Yamaoka, Kunihiro ; Kubo, Satoshi ; Tanaka, Yoshiya ; Maeshima, Keisuke. / Regulation of inflammation through JAK3-Stat6 pathway in dendritic cells. :: Japanese Journal of Clinical Immunology. 2012 ; 巻 35, 番号 1. pp. 62-68.
@article{5f01c804af4147a1a0fe87f4948213aa,
title = "Regulation of inflammation through JAK3-Stat6 pathway in dendritic cells",
abstract = "Dendritic cells (DCs) is the cell that act as source of the immune response by exquisitely presenting antigens to acquired immunity such as the T cells. Janus kinase (JAK) is a tyrosine kinase that is activated immediately after the cytokine binds to its unique receptor expressed on the cell surface. Among the JAKs, expression of JAK3 is limited on heamatopoietic cells and is indispensable for lymphocyte development and proliferation. We have demonstrated that JAK3-deficient DCs normally develop, uptake antigens, produce inflammatory cytokines and function as an antigen-presenting cell, although they over-produce IL-10. Among the transcription factors that are known to be activated by JAK3, we explored the phenotype of Stat6-deficient DCs which is a transcription factor specifically activated by JAK3. Interestingly, development, function and inflammatory cytokine production was normal with over-production of IL-10 which was in line with the JAK3Ideficient DCs. IL-4 is well known to activate JAK3-Stat6 in the cytoplasm and has been reported to be produced in the synovial fluid of rheumatoid arthritis patients. Hence the suppression of IL-10 production by IL-4 can be considered as one of the inflammatory process of arthritis. Moreover, induction of IL-10 production by DCs can be one mechanism of action of the JAK inhibitor (tofacitinib) which have shown high efficiency on active rheumatoid arthritis in clinical trials.",
keywords = "dendritic cells, JAK3, Stat6",
author = "Kunihiro Yamaoka and Satoshi Kubo and Yoshiya Tanaka and Keisuke Maeshima",
year = "2012",
doi = "10.2177/jsci.35.62",
language = "English",
volume = "35",
pages = "62--68",
journal = "Immunological Medicine",
issn = "0911-4300",
publisher = "Taylor and Francis Ltd.",
number = "1",

}

TY - JOUR

T1 - Regulation of inflammation through JAK3-Stat6 pathway in dendritic cells

AU - Yamaoka, Kunihiro

AU - Kubo, Satoshi

AU - Tanaka, Yoshiya

AU - Maeshima, Keisuke

PY - 2012

Y1 - 2012

N2 - Dendritic cells (DCs) is the cell that act as source of the immune response by exquisitely presenting antigens to acquired immunity such as the T cells. Janus kinase (JAK) is a tyrosine kinase that is activated immediately after the cytokine binds to its unique receptor expressed on the cell surface. Among the JAKs, expression of JAK3 is limited on heamatopoietic cells and is indispensable for lymphocyte development and proliferation. We have demonstrated that JAK3-deficient DCs normally develop, uptake antigens, produce inflammatory cytokines and function as an antigen-presenting cell, although they over-produce IL-10. Among the transcription factors that are known to be activated by JAK3, we explored the phenotype of Stat6-deficient DCs which is a transcription factor specifically activated by JAK3. Interestingly, development, function and inflammatory cytokine production was normal with over-production of IL-10 which was in line with the JAK3Ideficient DCs. IL-4 is well known to activate JAK3-Stat6 in the cytoplasm and has been reported to be produced in the synovial fluid of rheumatoid arthritis patients. Hence the suppression of IL-10 production by IL-4 can be considered as one of the inflammatory process of arthritis. Moreover, induction of IL-10 production by DCs can be one mechanism of action of the JAK inhibitor (tofacitinib) which have shown high efficiency on active rheumatoid arthritis in clinical trials.

AB - Dendritic cells (DCs) is the cell that act as source of the immune response by exquisitely presenting antigens to acquired immunity such as the T cells. Janus kinase (JAK) is a tyrosine kinase that is activated immediately after the cytokine binds to its unique receptor expressed on the cell surface. Among the JAKs, expression of JAK3 is limited on heamatopoietic cells and is indispensable for lymphocyte development and proliferation. We have demonstrated that JAK3-deficient DCs normally develop, uptake antigens, produce inflammatory cytokines and function as an antigen-presenting cell, although they over-produce IL-10. Among the transcription factors that are known to be activated by JAK3, we explored the phenotype of Stat6-deficient DCs which is a transcription factor specifically activated by JAK3. Interestingly, development, function and inflammatory cytokine production was normal with over-production of IL-10 which was in line with the JAK3Ideficient DCs. IL-4 is well known to activate JAK3-Stat6 in the cytoplasm and has been reported to be produced in the synovial fluid of rheumatoid arthritis patients. Hence the suppression of IL-10 production by IL-4 can be considered as one of the inflammatory process of arthritis. Moreover, induction of IL-10 production by DCs can be one mechanism of action of the JAK inhibitor (tofacitinib) which have shown high efficiency on active rheumatoid arthritis in clinical trials.

KW - dendritic cells

KW - JAK3

KW - Stat6

UR - http://www.scopus.com/inward/record.url?scp=85017552642&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017552642&partnerID=8YFLogxK

U2 - 10.2177/jsci.35.62

DO - 10.2177/jsci.35.62

M3 - Article

AN - SCOPUS:85017552642

VL - 35

SP - 62

EP - 68

JO - Immunological Medicine

JF - Immunological Medicine

SN - 0911-4300

IS - 1

ER -