2012 Fiscal Year Final Research Report
Induction of novel regulatory T cells by JAK inhibitor and its application for inflammatory disease treatment
| Project/Area Number |
23791105
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OKAMOTO Akiko 東京大学, 保健・健康推進本部, 助教 (40431861)
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| Project Period (FY) |
2011 – 2012
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| Keywords | JAK 阻害薬 / 制御性T細胞 / 全身性エリテマトーデス(systemic lupus erythematosus; SLE)コラーゲン誘導性関節炎 |
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| Research Abstract |
We have recently identified a novel regulatory T cells (Treg) population that expresses lymphocyte activation gene-3(LAG3) and early growth response gene-2(Egr2). LAG3+ Treg strongly suppress autoantibody production. Young DBA1J mice and lupus-prone NZB/W F1 mice had fewer LAG3+ Treg in the spleen compared with control B6mice. We found that in vivo tofacitinib, a JAK inhibitor, treatment increased ofCD4+CD25-LAG3+ regulatory cells in the spleen of B6 mice. We found that tofacitinib, a JAK inhibitor, induces LAG3+ Treg-like CD4+Egr2+ T cells (Tofa T cells) in vitro. Tofa T cells suppressed autoantibody production and nephritis progression in BWF1 mice. LAG3+ Treg and Tofa-T cells significantly suppressed the progression of collagen induced arthritis (CIA)in DBA1J mice. Tofacitinib conferred the expression of regulatory molecules and in vivo suppressive function on CD4+ T cells. The induction of LAG3+ Treg would contribute the regulation of chronic inflammatory diseases.
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