A role of regulatory B cell in psoriasis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17764
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kanazawa University
• Principal Investigator: Mizumaki Kie 金沢大学, 附属病院, 医員 (30802813)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 乾癬 / 制御性B細胞 / B細胞 / IL-23

Outline of Final Research Achievements

This study aimed to investigate the role of Regulatory B cells (Bregs) in a model of IL-23-mediated psoriasis-like inflammation in B cell-specific PTEN-deficient mice, in which Bregs are significantly expanded. IL-23-mediated psoriasis-like inflammation was suppressed in B cell-specific PTEN-deficient mice along with decreased ear thickness and epidermal thickness on day 15. mIL-23-injected B cell-specific PTEN-deficient mice showed expanded regulatory T cells (Tregs) in the spleen and draining lymph nodes along with increased Bregs. Further, T helper (Th) 17 differentiation in the rmIL-23-injected ear was suppressed in B cell-specific PTEN-deficient mice. Moreover, adoptive transfer of B1 B cells suppressed IL-23-mediated psoriasis-like inflammation. These results indicate that increased Bregs suppress IL-23-mediated psoriasis-like inflammation through Treg expansion and inhibition of Th17 differentiation. Thus, targeting Bregs may be a feasible treatment strategy for psoriasis.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

B細胞特異的PTEN欠損マウスでは、脾臓、所属リンパ節で増加した制御性B細胞が、ナイーブT細胞から制御性T細胞への分化を促進させ、皮膚病変部のTh17細胞への分化を抑制することでIL-23誘導性皮膚炎を抑制していると考えられた。本研究の結果により、B細胞特異的PTEN欠損マウスにおいて制御性B細胞が乾癬に対して抑制的に働く可能性が示唆され、制御性B細胞を標的とした治療が、乾癬の新たな治療戦略になる可能性が示された。