{"doi":"10.3389/fimmu.2022.883375","title":"Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus–Like Inflammation","abstract":"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.","journal":"Frontiers in Immunology","year":2022,"id":257622,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":908622,"name":"Purvi Mande","orcid":null,"position":1,"is_corresponding":false},{"id":908116,"name":"Tia Y. Brodeur","orcid":"0000-0001-6845-9350","position":2,"is_corresponding":false},{"id":908117,"name":"Kaiyuan Hao","orcid":"0000-0002-3862-6848","position":3,"is_corresponding":false},{"id":633405,"name":"Grace E. Ryan","orcid":null,"position":4,"is_corresponding":false},{"id":908623,"name":"Stephanie Moses","orcid":null,"position":5,"is_corresponding":false},{"id":908624,"name":"Sharon Subramanian","orcid":null,"position":6,"is_corresponding":false},{"id":908625,"name":"Xhuliana Picari","orcid":null,"position":7,"is_corresponding":false},{"id":616032,"name":"Khashayar Afshari","orcid":"0000-0001-9099-7948","position":8,"is_corresponding":false},{"id":533236,"name":"Ann Marshak‐Rothstein","orcid":"0000-0003-2136-8130","position":9,"is_corresponding":false},{"id":325326,"name":"Jillian M. Richmond","orcid":"0000-0003-1589-6770","position":10,"is_corresponding":false},{"id":650092,"name":"Nazgol‐Sadat Haddadi","orcid":"0000-0001-8854-8182","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:25:34.440699Z","pmid":"35833127","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}