Primary cilia prevent activation of the cGAS-STING pathway during mouse decidualization

• DOI: 10.1038/s42003-025-08030-x
• Publication Date: 2025-04-14T06:12:36Z
• Authors: Bo Li; Yu-Ying He; Wen-Xu Yao; Dan-Dan Jin; Hui-Na Luo; Meng-Yuan Li; Ying Wu; Zeng-Ming Yang
• Keywords: Sting; Decidualization; Primary (astronomy)

Primary cilia are antenna-like organelles that sense extracellular signals and function as signaling hubs essential for vertebrate development homeostasis. Decidualization is crucial pregnancy establishment maintenance in both humans mice. While primary present endometrial stromal cells, their role remains unknown. Here, we identify TMEM67, a key component of the ciliary transition zone, critical regulator mouse decidualization. Loss triggers RhoA-MLC2-dependent actomyosin contraction, which transmits mechanical forces to nuclear lamina, leading micronuclei formation. Within these micronuclei, double-stranded DNA (dsDNA) can directly bind cyclic GMP-AMP synthase (cGAS) situ, initiating downstream signaling. This activation cGAS-STING pathway reduces CCL6 production impairs Furthermore, pharmacological inhibition actin polymerization or RhoA-ROCK alleviates surrounding restores ciliogenesis, maintains integrity, suppresses activation, ultimately rescues Our findings reveal previously unrecognized mechanism by regulate cytoskeleton maintain integrity prevent leakage. safeguards against aberrant pathway, would otherwise trigger detrimental immune impair