Dichotomous Regulation of Group 3 Innate Lymphoid Cells by Non-gastric Helicobacter Species from an Immunocompromised Mouse

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 Helicobacter species, Helicobacter apodemus and Helicobacter typhlonius, isolated from immunocompromised mice. We demonstrated that the introduction of both Helicobacter species activated ILCs and induced gut inflammation; however, these Helicobacter 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 Helicobacter species, and may serve as a model for further investigations to elucidate the host-microbe interactions that critically sustain the maintenance of intestinal ILC3s. (1) RNA-seq (2 replicates) of whole proximal colon tissue from Rag1‒/‒ mice gavaged with Rag1‒/‒ and Rag1‒/‒ Selplg‒/‒ (RPS) feces; (2) 16S rRNA gene sequencing of fecal DNA from Rag1‒/‒ and RPS mice; (3) 16S rRNA gene sequencing of fecal DNA from Rag1‒/‒ mice gavaged with Rag1‒/‒ and RPS feces and treated with antibiotics.