中文摘要：胸腺基质淋巴细胞生成素（TSLP）是一种白介素-7（IL-7）样的细胞因子，能够参与T 细胞辅助2型免疫应答。本研究发现，当采用肺炎球菌表面蛋白A（PspA） 和霍乱毒素（CT）通过鼻腔免疫小鼠时，与单独使用肺炎球菌表面蛋白A（PspA）相比，小鼠粘膜性体内髓样树突状细胞内TSLP及其受体TSLPR的水平上调。在使用PspA + CT 粘膜免疫小鼠后，TSLPR基因敲除小鼠与野生小鼠相比，血液和粘膜中的PspA特异性IgA免疫反应显著降低，而IgG Ab反应没有变化。同时，采用PspA + CT 免疫后，TSLPR敲除小鼠体内CD11c(+)粘膜性体内髓样树突状细胞未被激活，与野生型小鼠相比，IgA-增强型细胞因子（APRIL、BAFF和IL-6）的表达水平显著降低。这些研究表明，TSLP-TSLPR信号通路在诱导粘膜性免疫反应对抗肺炎球菌感染方面具有关键作用。
 
外文摘要：Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7)-like cytokine involved in T helper 2 type immune responses. The primary target of TSLP is myeloid dendritic cells (DCs), however, little is known about the mechanism by which TSLP elicits respiratory IgA immune responses upon mucosal immunization. Here, we found that the levels of TSLP and TSLPR were upregulated in the mucosal DCs of mice nasally immunized with pneumococcal surface protein A (PspA) plus cholera toxin (CT) compared with those immunized with PspA alone. PspA-specific IgA responses, but not IgG Ab responses were significantly reduced in both serum and mucosal secretions of TSLPR knockout mice compared with wild-type mice after nasal immunization with PspA plus CT. Furthermore, CD11c(+) mucosal DCs isolated from TSLPR knockout mice nasally immunized with PspA plus CT were less activated and exhibited markedly reduced expression of IgA-enhancing cytokines (e.g., APRIL, BAFF, and IL-6) compared with those from equivalently immunized wild-type mice. Finally, exogenous TSLP promoted production of IgAs in an in vitro DC-B cell co-culture system as exhibited by enhanced IL-6 production. These results suggest that TSLP-TSLPR signaling is pivotal in the induction of nasal respiratory immunity against pathogenic pneumococcal infection.
外文关键词：THYMIC STROMAL LYMPHOPOIETIN; SURFACE PROTEIN-A; STREPTOCOCCUS-PNEUMONIAE; EPITHELIAL-CELLS; INTRANASAL IMMUNIZATION; PULMONARY INFECTION; B-CELLS; IMMUNITY; PSPA; MICE
作者：Joo, S; Fukuyama, Y; Park, E; Yuki, Y; Kurashima, Y; Ouchida, R; Ziegler, SF; Kiyono, H
作者单位：日本东北大学
期刊名称：MUCOSAL IMMUNOLOGY
期刊影响因子：7.748
出版年份：2017
出版刊次：7
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