Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus-Like Inflammation
Copyright © 2022 Haddadi, Mande, Brodeur, Hao, Ryan, Moses, Subramanian, Picari, Afshari, Marshak-Rothstein and Richmond..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Frontiers in immunology - 13(2022) vom: 14., Seite 883375 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Haddadi, Nazgol-Sadat [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
CD4+ helper T cell |
|---|
| Anmerkungen: |
Date Completed 15.07.2022 Date Revised 27.04.2023 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.3389/fimmu.2022.883375 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM343534533 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM343534533 | ||
| 003 | DE-627 | ||
| 005 | 20231226204959.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2022.883375 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1145.xml |
| 035 | |a (DE-627)NLM343534533 | ||
| 035 | |a (NLM)35833127 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Haddadi, Nazgol-Sadat |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus-Like Inflammation |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.07.2022 | ||
| 500 | |a Date Revised 27.04.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Haddadi, Mande, Brodeur, Hao, Ryan, Moses, Subramanian, Picari, Afshari, Marshak-Rothstein and Richmond. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a CD4+ helper T cell | |
| 650 | 4 | |a CXCR6 | |
| 650 | 4 | |a Lupus flare | |
| 650 | 4 | |a Th1 & Th2 | |
| 650 | 4 | |a cutaneous lupus erythematosus | |
| 650 | 7 | |a Interferon Regulatory Factors |2 NLM | |
| 650 | 7 | |a Irf5 protein, mouse |2 NLM | |
| 700 | 1 | |a Mande, Purvi |e verfasserin |4 aut | |
| 700 | 1 | |a Brodeur, Tia Y |e verfasserin |4 aut | |
| 700 | 1 | |a Hao, Kaiyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Ryan, Grace E |e verfasserin |4 aut | |
| 700 | 1 | |a Moses, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Subramanian, Sharon |e verfasserin |4 aut | |
| 700 | 1 | |a Picari, Xhuliana |e verfasserin |4 aut | |
| 700 | 1 | |a Afshari, Khashayar |e verfasserin |4 aut | |
| 700 | 1 | |a Marshak-Rothstein, Ann |e verfasserin |4 aut | |
| 700 | 1 | |a Richmond, Jillian M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d 2010 |g 13(2022) vom: 14., Seite 883375 |w (DE-627)NLM215811453 |x 1664-3224 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2022 |g day:14 |g pages:883375 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fimmu.2022.883375 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 13 |j 2022 |b 14 |h 883375 | ||