CD160-competent ILC2 are crucial for the ejection of intestinal helminths by the innate immune system

TY - JOUR

T1 - CD160-competent ILC2 are crucial for the ejection of intestinal helminths by the innate immune system

AU - Heepmann, Lennart

AU - Hartmann, Wiebke

AU - Linnemann, Lara

AU - Dörken, Sara

AU - Viebrock, Birte

AU - Orinska, Zane

AU - Jacobs, Thomas

AU - McSorley, Henry J.

AU - Breloer, Minka

N1 - Publisher Copyright: © 2026 The Author(s). Published by Elsevier Inc. on behalf of Society for Mucosal Immunology. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

PY - 2026/4/17

Y1 - 2026/4/17

N2 - 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.

AB - 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.

KW - Group 2 innate lymphoid cell

KW - Helminth

KW - Immune checkpoint molecule

KW - Immune regulation

KW - Intestine

KW - Mucosal mast cell

KW - Parasitic nematode

KW - Strongyloides ratti

KW - Type 2 immunity

UR - https://www.scopus.com/pages/publications/105036225825

U2 - 10.1016/j.mucimm.2026.04.005

DO - 10.1016/j.mucimm.2026.04.005

M3 - Article

C2 - 41974253

AN - SCOPUS:105036225825

SN - 1933-0219

JO - Mucosal Immunology

JF - Mucosal Immunology

ER -