| First Author | Mencarelli A | Year | 2018 |
| Journal | Front Immunol | Volume | 9 |
| Pages | 261 | PubMed ID | 29515579 |
| Mgi Jnum | J:286052 | Mgi Id | MGI:6391508 |
| Doi | 10.3389/fimmu.2018.00261 | Citation | Mencarelli A, et al. (2018) Calcineurin B in CD4(+) T Cells Prevents Autoimmune Colitis by Negatively Regulating the JAK/STAT Pathway. Front Immunol 9:261 |
| abstractText | Calcineurin (Cn) is a protein phosphatase that regulates the activation of the nuclear factor of activated T-cells (NFAT) family of transcription factors, which are key regulators of T-cell development and function. Here, we generated a conditional Cnb1 mouse model in which Cnb1 was specifically deleted in CD4(+) T cells (Cnb1(CD4) mice) to delineate the role of the Cn-NFAT pathway in immune homeostasis of the intestine. The Cnb1(CD4) mice developed severe, spontaneous colitis characterized at the molecular level by an increased T helper-1-cell response but an unaltered regulatory T-cell compartment. Antibiotic treatment ameliorated the intestinal inflammation observed in Cnb1(CD4) mice, suggesting that the microbiota contributes to the onset of colitis. CD4(+) T cells isolated from Cnb1(CD4) mice produced high levels of IFNgamma due to increased activation of the JAK2/STAT4 pathway induced by IL-12. Our data highlight that Cn signaling in CD4(+) T cells is critical for intestinal immune homeostasis in part by inhibiting IL-12 responsiveness of CD4(+) T cells. |
