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Inducer-like group 3 innate lymphoid cells (ILC3s) select microbiota-specific regulatory T cells to establish tolerance in the gut
Lyu M, Suzuki H, Kang L, et al. ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut. Nature 2022. doi: 10.1038/s41586-022-05141-x
Stimulation from the microbial population present in the GI tract induces immunological responses from T cells that have been suggested to be implicated in a variety of GI diseases, most notably IBD. In this study, Lyu et al used a murine model as well as human tissue from healthy controls and from patients with IBD to show that the T cells expressing the transcription factor retinoic acid–related orphan receptor gamma t (RORγt) play a critical role in maintaining the balance between a tolerogenic and inflammatory response to microbiota in the intestine. The analysis of RORγt+ immune cells isolated in the intestinal lymph nodes of mice reveals the predominance of a mixed population of T regulatory (Treg) cells and lymphoid tissue ILC3s. These ILC3s exhibit a distinct immunological profile and seem to perform a crucial function in promoting the development of the protolerogenic RORγt+ Treg cells while blocking the proliferation of proinflammatory T helper 17 cells. This effect is shown to be mediated via the mechanism of antigen presentation and the action of alpha V integrin. Interestingly, in human intestinal tissue, there is a positive correlation between ILC3s and RORγt+ Treg cells in the healthy intestine, while in contrast a dysregulation of these cell types is observed in IBD. Taken together, these results indicate that ILC3 disruption seems to result in the tilting of the balance towards inflammation rather than tolerance after microbiota-derived stimuli in the intestine, a process heavily involved in the pathogenesis of IBD.
Engineering of gut bacteria to impact on host physiology
Russell B, Brown S, Siguenza N, et al. Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes. Cell 2022; 185(17):3263–3277 doi: 10.1016/j.cell.2022.06.050.
As interest in the contribution …
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.