Intrarectal Immunization and IgA Antibody-Secreting Cell Homing to the Small Intestine
Intrarectal Immunization and IgA Antibody-Secreting Cell Homing to the Small Intestine
复制标题
DOI：
10.4049/jimmunol.1202979
复制
发表时间：
2013-05-01
影响因子：
4.4
通讯作者：
Pothier, Pierre
中科院分区：
文献类型：
--
作者：
Agnello, Davide;Denimal, Damien;Pothier, Pierre
根据目前的范例，淋巴细胞归巢到小肠需要两种组织特异性归巢受体的表达，整合素α（4）β（7）和CCL 25受体CCR 9。在这项研究中，我们调查的器官分布和归巢分子表达的伊加抗体分泌细胞（ASCs）诱导的直肠内免疫颗粒Ag，与其他粘膜免疫途径相比。直肠内免疫诱导肠道归巢伊加ASC，其不仅定位于结肠中，而且定位于小肠中，尽管它们不响应于CCL 25，不像通过口服免疫诱导的伊加ASC。粘膜上皮趋化因子CCL 28，已知吸引所有的伊加ASC，不补偿CCL 25的反应性的缺乏，因为Ag-特异性细胞的数量没有减少，在肠道中的CCR 10-缺陷小鼠通过直肠内途径免疫。然而，通过直肠内免疫诱导的Ag特异性伊加ASC表达整合素α（4）β（7），并且它们在通过直肠内途径免疫的β（7）缺陷小鼠的肠道中的数量显著减少，表明α（4）β（7）使这些细胞能够迁移到小肠中，即使没有CCL 25应答性。相比之下，通过鼻内免疫诱导的伊加ASC表达低α（4）β（7）水平，并且通常被排除在肠道之外。有趣的是，鼻内免疫后，Ag特异性伊加ASC在β 7缺陷小鼠的小肠中显著增加，表明淋巴细胞归巢是一个竞争性过程，整联蛋白α 4 β 7不仅决定了GALT中引发的伊加ASC的肠道向性，还决定了在其他诱导位点引发的淋巴细胞的肠道排斥。免疫学杂志，2013，190：4836-4847。
According to the current paradigm, lymphocyte homing to the small intestine requires the expression of two tissue-specific homing receptors, the integrin alpha(4)beta(7) and the CCL25 receptor CCR9. In this study, we investigated the organ distribution and the homing molecule expression of IgA Ab-secreting cells (ASCs) induced by intrarectal immunization with a particulate Ag, in comparison with other mucosal immunization routes. Intrarectal immunization induces gut-homing IgA ASCs that localize not only in the colon but also in the small intestine, although they are not responsive to CCL25, unlike IgA ASCs induced by oral immunization. The mucosal epithelial chemokine CCL28, known to attract all IgA ASCs, does not compensate for the lack of CCL25 responsiveness, because the number of Ag-specific cells is not decreased in the gut of CCR10-deficient mice immunized by the intrarectal route. However, Ag-specific IgA ASCs induced by intrarectal immunization express the integrin alpha(4)beta(7), and their number is considerably decreased in the gut of beta(7)-deficient mice immunized by the intrarectal route, indicating that alpha(4)beta(7) enables these cells to migrate into the small intestine, even without CCL25 responsiveness. In contrast, IgA ASCs induced by intranasal immunization express low alpha(4)beta(7) levels and are usually excluded from the gut. Paradoxically, after intranasal immunization, Ag-specific IgA ASCs are significantly increased in the small intestine of beta(7)-deficient mice, demonstrating that lymphocyte homing is a competitive process and that integrin alpha(4)beta(7) determines not only the intestinal tropism of IgA ASCs elicited in GALTs but also the intestinal exclusion of lymphocytes primed in other inductive sites. The Journal of Immunology, 2013, 190: 4836-4847.