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Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus–Like Inflammation

Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease characterized by a strong IFN signature, normally associated with type I IFNs. However, increasing evidence points to an additional role for IFNγ, or at least a pathogenic T effector subset dependent on IFNγ, for disease progression....

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Autores principales: Haddadi, Nazgol-Sadat, Mande, Purvi, Brodeur, Tia Y., Hao, Kaiyuan, Ryan, Grace E., Moses, Stephanie, Subramanian, Sharon, Picari, Xhuliana, Afshari, Khashayar, Marshak-Rothstein, Ann, Richmond, Jillian M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271959/
https://www.ncbi.nlm.nih.gov/pubmed/35833127
http://dx.doi.org/10.3389/fimmu.2022.883375
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author Haddadi, Nazgol-Sadat
Mande, Purvi
Brodeur, Tia Y.
Hao, Kaiyuan
Ryan, Grace E.
Moses, Stephanie
Subramanian, Sharon
Picari, Xhuliana
Afshari, Khashayar
Marshak-Rothstein, Ann
Richmond, Jillian M.
author_facet Haddadi, Nazgol-Sadat
Mande, Purvi
Brodeur, Tia Y.
Hao, Kaiyuan
Ryan, Grace E.
Moses, Stephanie
Subramanian, Sharon
Picari, Xhuliana
Afshari, Khashayar
Marshak-Rothstein, Ann
Richmond, Jillian M.
author_sort Haddadi, Nazgol-Sadat
collection PubMed
description Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease characterized by a strong IFN signature, normally associated with type I IFNs. However, increasing evidence points to an additional role for IFNγ, or at least a pathogenic T effector subset dependent on IFNγ, for disease progression. Nevertheless, Th2 effector subsets have also been implicated in CLE. We have now assessed the role of specific T cell subsets in the initiation and persistence of skin disease using a T cell-inducible murine model of CLE, dependent on KJ1-26 T cell recognition of an ovalbumin fusion protein. We found that only Th2-skewed cells, and not Th1-skewed cells, induced the development of skin lesions. However, we provide strong evidence that the Th2 disease-initiating cells convert to a more Th1-like functional phenotype in vivo by the time the skin lesions are apparent. This phenotype is maintained and potentiates over time, as T cells isolated from the skin, following a second induction of self-antigen, expressed more IFN-γ than T cells isolated at the time of the initial response. Transcriptional analysis identified additional changes in the KJ1-26 T cells at four weeks post injection, with higher expression levels of interferon stimulated genes (ISGs) including CXCL9, IRF5, IFIH1, and MX1. Further, injection of IFN-γ-/- T cells faied to induce skin disease in mice. We concluded that Th2 cells trigger skin lesion formation in CLE, and these cells switch to a Th1-like phenotype in the context of a TLR7-driven immune environment that is stable within the T cell memory compartment.
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spelling pubmed-92719592022-07-12 Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus–Like Inflammation Haddadi, Nazgol-Sadat Mande, Purvi Brodeur, Tia Y. Hao, Kaiyuan Ryan, Grace E. Moses, Stephanie Subramanian, Sharon Picari, Xhuliana Afshari, Khashayar Marshak-Rothstein, Ann Richmond, Jillian M. Front Immunol Immunology Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease characterized by a strong IFN signature, normally associated with type I IFNs. However, increasing evidence points to an additional role for IFNγ, or at least a pathogenic T effector subset dependent on IFNγ, for disease progression. Nevertheless, Th2 effector subsets have also been implicated in CLE. We have now assessed the role of specific T cell subsets in the initiation and persistence of skin disease using a T cell-inducible murine model of CLE, dependent on KJ1-26 T cell recognition of an ovalbumin fusion protein. We found that only Th2-skewed cells, and not Th1-skewed cells, induced the development of skin lesions. However, we provide strong evidence that the Th2 disease-initiating cells convert to a more Th1-like functional phenotype in vivo by the time the skin lesions are apparent. This phenotype is maintained and potentiates over time, as T cells isolated from the skin, following a second induction of self-antigen, expressed more IFN-γ than T cells isolated at the time of the initial response. Transcriptional analysis identified additional changes in the KJ1-26 T cells at four weeks post injection, with higher expression levels of interferon stimulated genes (ISGs) including CXCL9, IRF5, IFIH1, and MX1. Further, injection of IFN-γ-/- T cells faied to induce skin disease in mice. We concluded that Th2 cells trigger skin lesion formation in CLE, and these cells switch to a Th1-like phenotype in the context of a TLR7-driven immune environment that is stable within the T cell memory compartment. Frontiers Media S.A. 2022-06-27 /pmc/articles/PMC9271959/ /pubmed/35833127 http://dx.doi.org/10.3389/fimmu.2022.883375 Text en Copyright © 2022 Haddadi, Mande, Brodeur, Hao, Ryan, Moses, Subramanian, Picari, Afshari, Marshak-Rothstein and Richmond 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
Haddadi, Nazgol-Sadat
Mande, Purvi
Brodeur, Tia Y.
Hao, Kaiyuan
Ryan, Grace E.
Moses, Stephanie
Subramanian, Sharon
Picari, Xhuliana
Afshari, Khashayar
Marshak-Rothstein, Ann
Richmond, Jillian M.
Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus–Like Inflammation
title Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus–Like Inflammation
title_full Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus–Like Inflammation
title_fullStr Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus–Like Inflammation
title_full_unstemmed Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus–Like Inflammation
title_short Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus–Like Inflammation
title_sort th2 to th1 transition is required for induction of skin lesions in an inducible and recurrent murine model of cutaneous lupus–like inflammation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271959/
https://www.ncbi.nlm.nih.gov/pubmed/35833127
http://dx.doi.org/10.3389/fimmu.2022.883375
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