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Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata
Here, we have explored the involvement of innate lymphoid cells-type 1 (ILC1) in the pathogenesis of alopecia areata (AA), because we found them to be significantly increased around lesional and non-lesional HFs of AA patients. To further explore these unexpected findings, we first co-cultured autol...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023162/ https://www.ncbi.nlm.nih.gov/pubmed/36930216 http://dx.doi.org/10.7554/eLife.80768 |
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author | Laufer Britva, Rimma Keren, Aviad Bertolini, Marta Ullmann, Yehuda Paus, Ralf Gilhar, Amos |
author_facet | Laufer Britva, Rimma Keren, Aviad Bertolini, Marta Ullmann, Yehuda Paus, Ralf Gilhar, Amos |
author_sort | Laufer Britva, Rimma |
collection | PubMed |
description | Here, we have explored the involvement of innate lymphoid cells-type 1 (ILC1) in the pathogenesis of alopecia areata (AA), because we found them to be significantly increased around lesional and non-lesional HFs of AA patients. To further explore these unexpected findings, we first co-cultured autologous circulating ILC1-like cells (ILC1lc) with healthy, but stressed, organ-cultured human scalp hair follicles (HFs). ILClc induced all hallmarks of AA ex vivo: they significantly promoted premature, apoptosis-driven HF regression (catagen), HF cytotoxicity/dystrophy, and most important for AA pathogenesis, the collapse of the HFs physiological immune privilege. NKG2D-blocking or IFNγ-neutralizing antibodies antagonized this. In vivo, intradermal injection of autologous activated, NKG2D+/IFNγ-secreting ILC1lc into healthy human scalp skin xenotransplanted onto SCID/beige mice sufficed to rapidly induce characteristic AA lesions. This provides the first evidence that ILC1lc, which are positive for the ILC1 phenotype and negative for the classical NK markers, suffice to induce AA in previously healthy human HFs ex vivo and in vivo, and further questions the conventional wisdom that AA is always an autoantigen-dependent, CD8 +T cell-driven autoimmune disease. |
format | Online Article Text |
id | pubmed-10023162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-100231622023-03-18 Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata Laufer Britva, Rimma Keren, Aviad Bertolini, Marta Ullmann, Yehuda Paus, Ralf Gilhar, Amos eLife Immunology and Inflammation Here, we have explored the involvement of innate lymphoid cells-type 1 (ILC1) in the pathogenesis of alopecia areata (AA), because we found them to be significantly increased around lesional and non-lesional HFs of AA patients. To further explore these unexpected findings, we first co-cultured autologous circulating ILC1-like cells (ILC1lc) with healthy, but stressed, organ-cultured human scalp hair follicles (HFs). ILClc induced all hallmarks of AA ex vivo: they significantly promoted premature, apoptosis-driven HF regression (catagen), HF cytotoxicity/dystrophy, and most important for AA pathogenesis, the collapse of the HFs physiological immune privilege. NKG2D-blocking or IFNγ-neutralizing antibodies antagonized this. In vivo, intradermal injection of autologous activated, NKG2D+/IFNγ-secreting ILC1lc into healthy human scalp skin xenotransplanted onto SCID/beige mice sufficed to rapidly induce characteristic AA lesions. This provides the first evidence that ILC1lc, which are positive for the ILC1 phenotype and negative for the classical NK markers, suffice to induce AA in previously healthy human HFs ex vivo and in vivo, and further questions the conventional wisdom that AA is always an autoantigen-dependent, CD8 +T cell-driven autoimmune disease. eLife Sciences Publications, Ltd 2023-03-17 /pmc/articles/PMC10023162/ /pubmed/36930216 http://dx.doi.org/10.7554/eLife.80768 Text en © 2023, Laufer Britva, Keren et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Laufer Britva, Rimma Keren, Aviad Bertolini, Marta Ullmann, Yehuda Paus, Ralf Gilhar, Amos Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata |
title | Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata |
title_full | Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata |
title_fullStr | Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata |
title_full_unstemmed | Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata |
title_short | Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata |
title_sort | involvement of ilc1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023162/ https://www.ncbi.nlm.nih.gov/pubmed/36930216 http://dx.doi.org/10.7554/eLife.80768 |
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