Redundant role of chemokines CCL25/TECK and CCL28/MEC in IgA+ plasmablast recruitment to the intestinal lamina propria after rotavirus infection
Redundant role of chemokines CCL25/TECK and CCL28/MEC in IgA+ plasmablast recruitment to the intestinal lamina propria after rotavirus infection
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DOI：
10.4049/jimmunol.176.10.5749
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发表时间：
2006-05-15
影响因子：
4.4
通讯作者：
Greenberg, Harry B.
中科院分区：
文献类型：
--
作者：
Feng, Ningguo;Jaimes, Maria C.;Greenberg, Harry B.
轮状病毒(RV)是儿童严重腹泻疾病的最重要原因。在乳鼠中，轮状病毒感染后不久，小肠固有层(LP)中总的和病毒特异性的IgA(+)浆母细胞增加，为研究IgA(+)细胞在小肠中的募集机制提供了独特的机会。在这项研究中，我们证明RV感染后LP中总的和RV特异性的IgA(+)浆母细胞的增加可以被联合应用14种抗趋化因子CCL25和CCL28的抗体所阻断，但不能单独使用任何一种抗体。在CCR9基因敲除小鼠中，RV感染仍可诱导IgA的浆母细胞在LP中显著积聚，并可被抗CCL28抗体阻断，证实了CCL25和CCL28的协同作用。联合抗趋化因子治疗后LP中没有IgA(+)浆母细胞积聚不是由于这些细胞的增殖或凋亡的变化。我们还发现，抗CCL25和抗CCL28单抗与抗-α，单抗联合应用不能进一步抑制IgA(+)细胞在LP中的聚集，CCL25受体CCR9与肠道归巢受体α(4)β(7)在IgA(+)浆母细胞上共表达。最后，我们发现RV感染与小肠中CCL25和CCL28的增加有关。因此，我们的发现表明，α(4)β(7)与CCR9或CCR10一起足以在轮状病毒感染期间介导IgA(+)浆母细胞的肠道迁移。
Rotaviruses (RV) are the most important cause of severe childhood diarrheal disease. In suckling mice, infection with RV results in an increase in total and virus-specific IgA(+) plasmablasts in the small intestinal lamina propria (LP) soon after infection, providing a unique opportunity to study the mechanism of IgA(+) cell recruitment into the small intestine. In this study, we show that the increase in total and RV-specific IgA(+) plasmablasts in the LP after RV infection can be blocked by the combined 14 administration of Abs against chemokines CCL25 and CCL28, but not by the administration of either Ab alone. RV infection in CCR9 knockout mice still induced a significant accumulation of IgA' plasmablasts in the LP, which was blocked by the addition of anti-CCL28 Ab, confirming the synergistic role of CCL25 and CCL28. The absence of IgA(+) plasmablast accumulation in LP following combined anti-chemokine treatment was not due to changes in proliferation or apoptosis in these cells. We also found that coadministration of anti-CCL25 and anti-CCL28 Abs with the addition of anti-alpha, Ab did not further inhibit IgA(+) cell accumulation in the LP and that the CCL25 receptor, CCR9, was coexpressed with the intestinal homing receptor alpha(4)beta(7), on IgA(+) plasmablasts. Finally, we showed that RV infection was associated with an increase in both CCL25 and CCL28 in the small intestine. Hence, our findings indicate that alpha(4)beta(7), along with either CCR9 or CCR10 are sufficient for mediating the intestinal migration of IgA(+) plasmablasts during RV infection.