IgA是哺乳动物分泌最多的抗体，在维持肠道稳态和粘膜屏障的功能上发挥重要作用。IgA的异常与肠道疾病（如炎症性肠病）密切相关，然而IgA的分泌调控机制目前并不清楚。我们前期实验发现，MZB1缺陷小鼠血清IgA水平显著下降，但IgG正常，并且体外实验发现MZB1缺陷影响浆细胞的IgA分泌，但不影响IgG的分泌。我们还发现腹腔注射LPS后，MZB1缺陷小鼠分泌到肠道的IgA量降低到野生型小鼠的20%以下。这些结果提示，MZB1促进IgA的分泌和肠道转运。本项目拟通过体内外实验全面阐明B细胞特异性MZB1在调控IgA分泌中的作用及分子机制。我们还计划研究MZB1能否通过促进IgA分泌抑制肠道炎症，并初步探讨IgA用于治疗炎症性肠病的可行性。本研究为进一步理解炎症性肠炎的发病机制提供新的视点。

IgA is the most abundantly produced antibody in mammalian species and plays a crucial role in maintaining gut homeostasis and normal mucosal barrier. Abnormalities in IgA function is closely associated with intestinal diseases such as inflammatory bowel diseases. How IgA secretion is regulated, however, remains largely unknown. We found that MZB1-deficienct mice had significantly decreased levels of serum IgA but normal IgG levels. In vitro studies revealed that MZB1 deficiency attenuated the secretion of IgA, but not IgG, by plasma cells. In addition, we found that MZB1-deficient mice were impaired in secreting large amounts of IgA into the gut in response to LPS stimulation. These observations suggest an important role for MZB1 in IgA secretion and gut transcytosis. The present study aims to clarify the role and molecular mechanism of MZB1 in regulating IgA secretion using both in vitro and in vivo approaches. We will also investigate whether MZB1 suppresses gut inflammation by promoting IgA secretion and explore the feasibility of using IgA to treat intestinal diseases. The present study should provide new insights in understanding the mechanism underlying inflammatory bowel disease.