IL-22及产生IL-22的Th22细胞能显著增强巨噬细胞杀灭结核菌的能力，在结核病免疫保护中起重要作用，阐明IL-22应答的调节机制是靶向IL-22免疫治疗结核病的理论基础。我们的前期研究发现，结核患者显著增多的CD19+CD5+CD1d+ B细胞对结核菌特异性IL-22应答的抑制是一个重要的调节途径，但目前尚不清楚抑制作用的具体机制。本项目拟进一步探讨B细胞对产生IL-22的细胞在细胞增殖、凋亡和迁移功能的调节作用；在此基础上，采用Transwell和特异性抗体阻断试验，明确细胞接触和IL-10/IL-4/TGF-β细胞因子在B细胞免疫抑制中的作用；通过分析B细胞对树突状细胞和CD4+CD25+FoxP3+调节性T细胞（Treg）功能的影响，结合细胞消除试验，明确树突状细胞和Treg在B细胞抑制IL-22应答中的作用和可能机制。从而为靶向IL-22的结核病免疫治疗和预防提供干预靶点。

Mycobacterium tuberculosis (mtb) infection induces high IL-22 and Th22 cell reponses. IL-22 and Th22 have been demonstrated to enhance the anti-microbial activity of macrophage, indicating that they play an important role in protective immunity. Therefore, illustrating regulatory mechanisms of IL-22 response during mycobacterium tuberculosis infection is important for clinical use of IL-22 for prevention and treatment of tuberculosis. Our previous findings showed that CD19+CD5+CD1d+ B cells (Breg) are increased in patients with tuberculosis. Depletion of Breg resulted in significant increase of mycobacterium tuberculosis antigen-specific IL-22 production by perpheral blood mononuclear cells (PBMC).In addition, purified Breg inhibits mtb-specific IL-22 production by B cell-depleted PBMCs. Moreover, the frequency of Breg in PBMCs is significantly higher in patients with tuberculosis than in healthy control and individuals with latent tuberculosis infection. Thus, these data indicated that Breg inhibition is an important mechanism in regulating antigen-specific IL-22 response in patients with TB. However, it remains to be elucidated how Breg regulate antigen-specific IL-22 response. In this study, we will first investigate the effect of Breg on cell death/apopotosis, cell proliferation, and migration of IL-22-producing cells. Second, we will investigate the role of cell-cell contact, cytokine IL-10/IL-4/TGF-beta in Breg regulation of IL-22 response. Third, we will investigate the effect of Breg on dendritic cells and its potential on regulating IL-22 responses. In doing these, we will define the mechanims underlying the regulation of antigen-specific IL-22 response by breg. Our findings in this study will provide new insight for immunotherapy and vaccine design against tuberculosis targeting IL-22 response.