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Title: Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway
Authors: Mencarelli, Andrea
Vacca, Maurizio
Khameneh, Hanif Javanmard
Acerbi, Enzo
Tay, Alicia
Zolezzi, Francesca
Poidinger, Michael
Mortellaro, Alessandra
Keywords: Calcineurin B
Nuclear Factor of Activated T Cell
Issue Date: 2018
Source: Mencarelli, A., Vacca, M., Khameneh, H. J., Acerbi, E., Tay, A., Zolezzi, F., et al. (2018). Calcineurin B in CD4+ T cells prevents autoimmune colitis by negatively regulating the JAK/STAT pathway. Frontiers in Immunology, 9, 261-.
Series/Report no.: Frontiers in Immunology
Abstract: 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 (Cnb1CD4 mice) to delineate the role of the Cn–NFAT pathway in immune homeostasis of the intestine. The Cnb1CD4 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 Cnb1CD4 mice, suggesting that the microbiota contributes to the onset of colitis. CD4+ T cells isolated from Cnb1CD4 mice produced high levels of IFNγ 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.
DOI: 10.3389/fimmu.2018.00261
Rights: © 2018 Mencarelli, Vacca, Khameneh, Acerbi, Tay, Zolezzi, Poidinger and Mortellaro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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