Dichotomous regulation of group 3 innate lymphoid cells by nongastric <i>Helicobacter</i> species

Abstract

Intestinal innate lymphoid cells (ILCs) contribute to the protective immunity and homeostasis of the gut, and the microbiota are critically involved in shaping ILC function. However, the role of the gut microbiota in regulating ILC development and maintenance still remains elusive. Here, we identified opposing effects on ILCs by two <i>Helicobacter</i> species, <i>Helicobacter apodemus</i> and <i>Helicobacter typhlonius</i>, isolated from immunocompromised mice. We demonstrated that the introduction of both <i>Helicobacter</i> species activated ILCs and induced gut inflammation; however, these <i>Helicobacter</i> species negatively regulated RORγt⁺ group 3 ILCs (ILC3s), especially T-bet⁺ ILC3s, and diminished their proliferative capacity. Thus, these findings underscore a previously unknown dichotomous regulation of ILC3s by <i>Helicobacter</i> species, and may serve as a model for further investigations to elucidate the host-microbe interactions that critically sustain the maintenance of intestinal ILC3s.