T-bet controls intestinal mucosa immune responses via repression of type 2 innate lymphoid cell function

Innate lymphoid cells (ILCs) play an important role in regulating immune responses at
mucosal surfaces. The transcription factor T -bet is crucial for the function of ILC1s and
NCR+ ILC3s and constitutive deletion of T-bet prevents the development of these
subsets. Lack of T-bet in the absence of an adaptive immune system, microbiota
dependent colitis occurs due to aberrant ILC3 responses, thus T-bet expression in the
innate immune system has been considered to dampen pathogenic immune responses.
Here we show that T-bet plays an unexpected role in negatively regulating innate type 2
responses, in the context of an otherwise intact immune system. Selective loss of T -bet
in ILCs leads to the expansion and increased activity of ILC2s, which has a functionally
important impact on mucosal immunity, including enhanced protection from Trichinella
spiralis infection and inflammatory colitis. Mechanistically, we show that T-bet controls
the intestinal ILC pool through regulation of IL7 receptor signalling. These data
demonstrate that T-bet expression in ILCs acts as the key transcriptional checkpoint in regulating pathogenic versus protective mucosal immune responses, which has
significant implications for the understanding of the pathogenesis of inflammatory
bowel diseases and intestinal infections.