Involvement of the JAK-STAT pathway in collagen regulation of decidual NK cells
Involvement of the JAK-STAT pathway in collagen regulation of decidual NK cells
复制标题
JAK-STAT 通路参与蜕膜 NK 细胞的胶原调节
DOI：
10.1111/aji.12769
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发表时间：
2017-12-01
影响因子：
3.6
通讯作者：
Li, Dajin
中科院分区：
文献类型：
--
作者：
Fu, Qiang;Sun, Yufei;Li, Dajin
问题：蜕膜自然杀伤细胞(DNKs)在母胎界面的调节机制尚不清楚。研究方法：将原代滋养层细胞(TROS)、蜕膜基质细胞(DSCs)和dNKs共同培养，并观察其对LAIR-2(LAIR-1抑制剂)和P4HshRNA(胶原抑制物)的反应。结果：dNKs与原代TROS/DSCs共培养可下调其Th1细胞因子的产生。这些作用可被LAIR-2和P4H shRNA消除。LAIR-1与SHP-1结合，SHP-1又与JAK1和JAK2结合。结论：JAK-STAT通路及其下游转录因子T-bet和Helios参与了胶原/LAIR-1相互作用对DNK功能的调节，这一信号机制可能参与了母胎界面免疫耐受的维持。
Problem: The mechanisms underlying the regulation of decidual natural killer cells (dNKs) at the maternal-fetal interface are unclear.Method of study: Primary trophoblasts (TROs), decidual stromal cells (DSCs), and dNKs were cocultured, and responses to LAIR-2 (LAIR-1 inhibitor) and P4H shRNA (collagen inhibitor) were studied.Results: Coculture of dNKs with primary TROs/DSCs resulted in downregulation of Th1 cytokine production by dNKs. These effects were abrogated by LAIR-2 and P4H shRNA. LAIR-1 binds to SHP-1, which in turn binds to JAK1 and JAK2. Further, the phosphorylation of STAT1/STAT4 and the expression of the downstream transcription factors T-bet and Helios in dNKs were decreased by collagen treatment and primary TROs/DSCs coculture.Conclusion: The JAK-STAT pathway and its downstream transcription factors T-bet and Helios are involved in the regulation of dNK function by collagen/LAIR-1 interaction, and this signaling mechanism may contribute to the maintenance of immune tolerance at the maternal-fetal interface.