Mucosal Immunol. 2026 Apr 11:S1933-0219(26)00042-5. doi: 10.1016/j.mucimm.2026.04.005. Online ahead of print.
ABSTRACT
1.6 billion people are currently infected with parasitic worms. Group 2 innate lymphoid cells (ILC2) play a central role in promoting the protective type 2 immunity against these parasites. Here we show that a subpopulation of intestinal ILC2 express the immune checkpoint molecule CD160 in mice infected with the parasitic nematode Strongyloides ratti. CD160+ ILC2 represented a distinct ST2–IL-17RB+Ki-67+ subset that expanded in vivo during S. ratti infection. By contrast, CD160– ILC2 were ST2+IL-17RB–Ki-67– and represented the dominant producers of type 2 cytokines. Upon in vitro stimulation, sorted CD160+ ILC2 progressively lost CD160 expression and acquired cytokine-producing capacity. While CD160-competent RAG KO mice efficiently controlled S. ratti infection with less than 1% of the infective dose remaining by day 10 post-infection, CD160-deficient RAG KO mice failed to expand intestinal ILC2, failed to activate mucosal mast cells and retained high intestinal worm burden for nearly 100 days. Adoptive transfer of CD160-competent ILC2 into S. ratti-infected CD160-deficient RAG KO mice partially restored mast cell activation and reduced intestinal worm burden by 50%. Collectively, these findings identify CD160 expression as a critical checkpoint in the development and expansion of fully functional ILC2 required for effective immunity against intestinal helminth infection.
PMID:41974253 | DOI:10.1016/j.mucimm.2026.04.005