Lazarus Nicole H, Kunkel Eric J, Johnston Brent, Wilson Eric, Youngman Kenneth R, Butcher Eugene C
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
J Immunol. 2003 Apr 1;170(7):3799-805. doi: 10.4049/jimmunol.170.7.3799.
IgA immunoblasts can seed both intestinal and nonintestinal mucosal sites following localized mucosal immunization, an observation that has led to the concept of a common mucosal immune system. In this study, we demonstrate that the mucosae-associated epithelial chemokine, MEC (CCL28), which is expressed by epithelia in diverse mucosal tissues, is selectively chemotactic for IgA Ab-secreting cells (ASC): MEC attracts IgA- but not IgG- or IgM-producing ASC from both intestinal and nonintestinal lymphoid and effector tissues, including the intestines, lungs, and lymph nodes draining the bronchopulmonary tree and oral cavity. In contrast, the small intestinal chemokine, TECK (CCL25), attracts an overlapping subpopulation of IgA ASC concentrated in the small intestines and its draining lymphoid tissues. Surprisingly, T cells from mucosal sites fail to respond to MEC. These findings suggest a broad and unifying role for MEC in the physiology of the mucosal IgA immune system.
局部黏膜免疫后,IgA免疫母细胞可在肠道和非肠道黏膜部位定植,这一观察结果引出了共同黏膜免疫系统的概念。在本研究中,我们证明黏膜相关上皮趋化因子MEC(CCL28),由多种黏膜组织的上皮细胞表达,对分泌IgA抗体的细胞(ASC)具有选择性趋化作用:MEC吸引来自肠道和非肠道淋巴组织及效应组织(包括肠道、肺以及引流支气管肺树和口腔的淋巴结)的分泌IgA而非IgG或IgM的ASC。相比之下,小肠趋化因子TECK(CCL25)吸引集中在小肠及其引流淋巴组织中的一部分重叠的IgA ASC亚群。令人惊讶的是,来自黏膜部位的T细胞对MEC无反应。这些发现表明MEC在黏膜IgA免疫系统生理过程中具有广泛而统一的作用。