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.
Keywords: JAK-STAT; LAIR-1; collagen; decidual NK cells.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.