Calcineurin B in CD4 T cells prevents autoimmune colitis by by negatively regulating the JAK/STAT pathway. Mus musculus

Nuclear factor of activated T-cells (NFAT) are a family of transcription factors, which are regulated by the calcium-sensing protein calmodulin and protein phosphatase Calcineurin. The different NFAT family members can have overlapping functions but also are now known to exhibit distinct functions in T cells and can influence host tolerance. In the current study, we investigated for the first time the role played by the calcineurin B (Cnb1) signaling in CD4 T cells. We generated mice that lack selectively Cnb1 in CD4 T cells (Cnb1CD4 mice) and analyzed the immune phenotype during the ageing and in vitro studies. Disruption of CnB signal in CD4 T cells was associated with an increase of IFNγ- and IL-17-secreting cells. Antibiotic treatment reverted the spontaneous intestinal inflammation observed in Cnb1CD4 mice, indicating that microbiota is the main factor involved in colitis onset. Our data indicate that Cnb1 pathway in CD4 T cells is fundamental to maintain immune homeostasis in the colon Overall design: Lamina Propria (LP)-colon CD45+CD3+CD4+CD44low cells were sorted from control group (CD4neg/Cnb1flox) and conditional (CD4cre/Cnb1flox) mice ( 3 independent experiments 3-5 mice/group). In particular in intestinal CD4+ T cells not fully differentiated the global gene expression analysis revealed that Cnb1 is an intrinsic negative regulator of a set of genes associated of Th1 polarization.