Cathepsin W restrains peripheral regulatory T cells for mucosal immune quiescence

Peripheral regulatory T (pT(reg)) cells are a key T cell lineage for mucosal immune tolerance and anti-inflammatory responses, and interleukin-2 receptor (IL-2R) signaling is critical for T(reg) cell generation, expansion, and maintenance. The expression of IL-2R on pT(reg) cells is tightly regulate...

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Autores principales: Li, Jian, Chen, Zuojia, Kim, Girak, Luo, Jialie, Hori, Shohei, Wu, Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Biomedicine and Life Sciences
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337914/
https://www.ncbi.nlm.nih.gov/pubmed/37436991
http://dx.doi.org/10.1126/sciadv.adf3924
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author Li, Jian
Chen, Zuojia
Kim, Girak
Luo, Jialie
Hori, Shohei
Wu, Chuan
author_facet Li, Jian
Chen, Zuojia
Kim, Girak
Luo, Jialie
Hori, Shohei
Wu, Chuan
author_sort Li, Jian
collection PubMed
description Peripheral regulatory T (pT(reg)) cells are a key T cell lineage for mucosal immune tolerance and anti-inflammatory responses, and interleukin-2 receptor (IL-2R) signaling is critical for T(reg) cell generation, expansion, and maintenance. The expression of IL-2R on pT(reg) cells is tightly regulated to ensure proper induction and function of pT(reg) cells without a clear molecular mechanism. We here demonstrate that Cathepsin W (CTSW), a cysteine proteinase highly induced in pT(reg) cells under transforming growth factor–β stimulation is essential for the restraint of pT(reg) cell differentiation in an intrinsic manner. Loss of CTSW results in elevated pT(reg) cell generation, protecting the animals from intestinal inflammation. Mechanistically, CTSW inhibits IL-2R signaling in pT(reg) cells by cytosolic interaction with and process of CD25, repressing signal transducer and activator of transcription 5 activation to restrain pT(reg) cell generation and maintenance. Hence, our data indicate that CTSW acts as a gatekeeper to calibrate pT(reg) cell differentiation and function for mucosal immune quiescence.
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spelling pubmed-103379142023-07-13 Cathepsin W restrains peripheral regulatory T cells for mucosal immune quiescence Li, Jian Chen, Zuojia Kim, Girak Luo, Jialie Hori, Shohei Wu, Chuan Sci Adv Biomedicine and Life Sciences Peripheral regulatory T (pT(reg)) cells are a key T cell lineage for mucosal immune tolerance and anti-inflammatory responses, and interleukin-2 receptor (IL-2R) signaling is critical for T(reg) cell generation, expansion, and maintenance. The expression of IL-2R on pT(reg) cells is tightly regulated to ensure proper induction and function of pT(reg) cells without a clear molecular mechanism. We here demonstrate that Cathepsin W (CTSW), a cysteine proteinase highly induced in pT(reg) cells under transforming growth factor–β stimulation is essential for the restraint of pT(reg) cell differentiation in an intrinsic manner. Loss of CTSW results in elevated pT(reg) cell generation, protecting the animals from intestinal inflammation. Mechanistically, CTSW inhibits IL-2R signaling in pT(reg) cells by cytosolic interaction with and process of CD25, repressing signal transducer and activator of transcription 5 activation to restrain pT(reg) cell generation and maintenance. Hence, our data indicate that CTSW acts as a gatekeeper to calibrate pT(reg) cell differentiation and function for mucosal immune quiescence. American Association for the Advancement of Science 2023-07-12 /pmc/articles/PMC10337914/ /pubmed/37436991 http://dx.doi.org/10.1126/sciadv.adf3924 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Li, Jian
Chen, Zuojia
Kim, Girak
Luo, Jialie
Hori, Shohei
Wu, Chuan
Cathepsin W restrains peripheral regulatory T cells for mucosal immune quiescence
title Cathepsin W restrains peripheral regulatory T cells for mucosal immune quiescence
title_full Cathepsin W restrains peripheral regulatory T cells for mucosal immune quiescence
title_fullStr Cathepsin W restrains peripheral regulatory T cells for mucosal immune quiescence
title_full_unstemmed Cathepsin W restrains peripheral regulatory T cells for mucosal immune quiescence
title_short Cathepsin W restrains peripheral regulatory T cells for mucosal immune quiescence
title_sort cathepsin w restrains peripheral regulatory t cells for mucosal immune quiescence
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337914/
https://www.ncbi.nlm.nih.gov/pubmed/37436991
http://dx.doi.org/10.1126/sciadv.adf3924
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