CYTIP promotes pro-inflammatory activation of microglia through interaction with LRRFIP2 following ischemic stroke

Yang, Zhihao, Wang, Yiqi, Zhou, Yuneng, Zhang, Ruolin, Liu, Chang, Bao, Wendai, Qin, Jun, Zhou, Peiyang, Li, Guangqiang, Duan, Chao, Dong, Jiawen, Wang, Haipeng, Zhang, Min, Yang, Xin ORCID: https://orcid.org/0000-0002-8429-7598, Shui, Ke and Dong, Zhiqiang 2026. CYTIP promotes pro-inflammatory activation of microglia through interaction with LRRFIP2 following ischemic stroke. Cellular Signalling , 112929. 10.1016/j.cellsig.2026.112929

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Abstract

Microglia-mediated neuroinflammation is a critical contributor to cerebral ischemia/reperfusion (I/R) injury. However, the functional heterogeneity of microglia presents significant challenges in defining therapeutic signatures. By integrating single-nucleus RNA sequencing (snRNA-seq) of a mouse middle cerebral artery occlusion/reperfusion (MCAO/R) model with bulk RNA sequencing of BV2 microglia subjected to oxygen-glucose deprivation/reoxygenation (OGD/R), we identified Cytip as a highly upregulated core regulator within a transient “primed” microglial subpopulation upon I/R insult. Functional validation demonstrated that Cytip promotes a pro-inflammatory microglial phenotype and exacerbates oxidative stress, whereas its knockdown ameliorates these OGD/R-induced dysfunctions. Mechanistically, immunoprecipitation–mass spectrometry revealed that CYTIP directly interacts with LRRFIP2. Overexpression of LRRFIP2 counteracted CYTIP-mediated pathogenic effects, significantly suppressing microglial inflammation and IL-1β production. These findings suggest that CYTIP promotes microglial inflammatory responses via the NLRP3/LRRFIP2 axis, highlighting the CYTIP–LRRFIP2 interaction as a promising therapeutic target for post-stroke recovery.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Engineering
Publisher:	Elsevier
ISSN:	0898-6568
Date of Acceptance:	2 October 2026
Last Modified:	06 Oct 2026 11:29
URI:	https://orca.cardiff.ac.uk/id/eprint/190036

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