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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9513232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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