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CD1d-independent NK1.1(+) Treg cells are IL2-inducible Foxp3(+) T cells co-expressing immunosuppressive and cytotoxic molecules

Regulatory T cells (Treg) play pivotal roles in maintaining self-tolerance and preventing immunological diseases such as allergy and autoimmunity through their immunosuppressive properties. Although Treg cells are heterogeneous populations with distinct suppressive functions, expression of natural k...

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Autores principales: Park, Hyun Jung, Lee, Sung Won, Park, Yun Hoo, Kim, Tae-Cheol, Van Kaer, Luc, Hong, Seokmann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513232/
https://www.ncbi.nlm.nih.gov/pubmed/36177042
http://dx.doi.org/10.3389/fimmu.2022.951592
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author Park, Hyun Jung
Lee, Sung Won
Park, Yun Hoo
Kim, Tae-Cheol
Van Kaer, Luc
Hong, Seokmann
author_facet Park, Hyun Jung
Lee, Sung Won
Park, Yun Hoo
Kim, Tae-Cheol
Van Kaer, Luc
Hong, Seokmann
author_sort Park, Hyun Jung
collection PubMed
description Regulatory T cells (Treg) play pivotal roles in maintaining self-tolerance and preventing immunological diseases such as allergy and autoimmunity through their immunosuppressive properties. Although Treg cells are heterogeneous populations with distinct suppressive functions, expression of natural killer (NK) cell receptors (NKR) by these cells remains incompletely explored. Here we identified that a small population of Foxp3(+)CD4(+) Treg cells in mice expresses the NK1.1 NKR. Furthermore, we found that rare NK1.1(+) subpopulations among CD4(+) Treg cells develop normally in the spleen but not the thymus through CD1d-independent pathways. Compared with NK1.1(-) conventional Treg cells, these NK1.1(+) Treg cells express elevated Treg cell phenotypic hallmarks, pro-inflammatory cytokines, and NK cell-related cytolytic mediators. Our results suggest that NK1.1(+) Treg cells are phenotypically hybrid cells sharing functional properties of both NK and Treg cells. Interestingly, NK1.1(+) Treg cells preferentially expanded in response to recombinant IL2 stimulation in vitro, consistent with their increased IL2Rαβ expression. Moreover, DO11.10 T cell receptor transgenic NK1.1(+) Treg cells were expanded in an ovalbumin antigen-specific manner. In the context of lipopolysaccharide-induced systemic inflammation, NK1.1(+) Treg cells downregulated immunosuppressive molecules but upregulated TNFα production, indicating their plastic adaptation towards a more pro-inflammatory rather than regulatory phenotype. Collectively, we propose that NK1.1(+) Treg cells might play a unique role in controlling inflammatory immune responses such as infection and autoimmunity.
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spelling pubmed-95132322022-09-28 CD1d-independent NK1.1(+) Treg cells are IL2-inducible Foxp3(+) T cells co-expressing immunosuppressive and cytotoxic molecules Park, Hyun Jung Lee, Sung Won Park, Yun Hoo Kim, Tae-Cheol Van Kaer, Luc Hong, Seokmann Front Immunol Immunology Regulatory T cells (Treg) play pivotal roles in maintaining self-tolerance and preventing immunological diseases such as allergy and autoimmunity through their immunosuppressive properties. Although Treg cells are heterogeneous populations with distinct suppressive functions, expression of natural killer (NK) cell receptors (NKR) by these cells remains incompletely explored. Here we identified that a small population of Foxp3(+)CD4(+) Treg cells in mice expresses the NK1.1 NKR. Furthermore, we found that rare NK1.1(+) subpopulations among CD4(+) Treg cells develop normally in the spleen but not the thymus through CD1d-independent pathways. Compared with NK1.1(-) conventional Treg cells, these NK1.1(+) Treg cells express elevated Treg cell phenotypic hallmarks, pro-inflammatory cytokines, and NK cell-related cytolytic mediators. Our results suggest that NK1.1(+) Treg cells are phenotypically hybrid cells sharing functional properties of both NK and Treg cells. Interestingly, NK1.1(+) Treg cells preferentially expanded in response to recombinant IL2 stimulation in vitro, consistent with their increased IL2Rαβ expression. Moreover, DO11.10 T cell receptor transgenic NK1.1(+) Treg cells were expanded in an ovalbumin antigen-specific manner. In the context of lipopolysaccharide-induced systemic inflammation, NK1.1(+) Treg cells downregulated immunosuppressive molecules but upregulated TNFα production, indicating their plastic adaptation towards a more pro-inflammatory rather than regulatory phenotype. Collectively, we propose that NK1.1(+) Treg cells might play a unique role in controlling inflammatory immune responses such as infection and autoimmunity. Frontiers Media S.A. 2022-09-13 /pmc/articles/PMC9513232/ /pubmed/36177042 http://dx.doi.org/10.3389/fimmu.2022.951592 Text en Copyright © 2022 Park, Lee, Park, Kim, Van Kaer and Hong https://creativecommons.org/licenses/by/4.0/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(s) 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.
spellingShingle Immunology
Park, Hyun Jung
Lee, Sung Won
Park, Yun Hoo
Kim, Tae-Cheol
Van Kaer, Luc
Hong, Seokmann
CD1d-independent NK1.1(+) Treg cells are IL2-inducible Foxp3(+) T cells co-expressing immunosuppressive and cytotoxic molecules
title CD1d-independent NK1.1(+) Treg cells are IL2-inducible Foxp3(+) T cells co-expressing immunosuppressive and cytotoxic molecules
title_full CD1d-independent NK1.1(+) Treg cells are IL2-inducible Foxp3(+) T cells co-expressing immunosuppressive and cytotoxic molecules
title_fullStr CD1d-independent NK1.1(+) Treg cells are IL2-inducible Foxp3(+) T cells co-expressing immunosuppressive and cytotoxic molecules
title_full_unstemmed CD1d-independent NK1.1(+) Treg cells are IL2-inducible Foxp3(+) T cells co-expressing immunosuppressive and cytotoxic molecules
title_short CD1d-independent NK1.1(+) Treg cells are IL2-inducible Foxp3(+) T cells co-expressing immunosuppressive and cytotoxic molecules
title_sort cd1d-independent nk1.1(+) treg cells are il2-inducible foxp3(+) t cells co-expressing immunosuppressive and cytotoxic molecules
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513232/
https://www.ncbi.nlm.nih.gov/pubmed/36177042
http://dx.doi.org/10.3389/fimmu.2022.951592
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