{"doi":"10.1186/s12974-024-03224-2","title":"IL-7Rα on CD4+ T cells is required for their survival and the pathogenesis of experimental autoimmune encephalomyelitis","abstract":"Abstract Background The IL-7 receptor alpha (IL-7Rα) binds both IL-7 and thymic stromal lymphopoietin (TSLP). IL-7Rα is essential for the development and survival of naive CD4 + T cells and their differentiation to effector/memory CD4 + T cells. Mice lacking IL-7Rα have severe lymphopenia and are resistant to experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. However, it has been reported that IL-7Rα on peripheral CD4 + T cells is disposable for their maintenance and EAE pathogenesis, which does not align with the body of knowledge on the role of IL-7Rα in the biology of CD4 + T cells. Given that a definitive study on this important topic is lacking, we revisited it using a novel approach, an inducible knockout of the IL-7Rα gene in CD4 + T cells. Methods We generated Il7ra fl/fl /CD4CreER T2 double transgenic mouse line (henceforth CD4 Δ Il7ra ), susceptible to tamoxifen-induced knockout of the IL-7Rα gene in CD4 + T cells. CD4 Δ Il7ra mice were immunized with MOG 35 − 55 for EAE induction and monitored for disease development. The expression of IL-7Rα, CD4 + T cell numbers, and MOG 35 − 55 -specific CD4 + T cell response was evaluated in the central nervous system (CNS) and lymphoid tissues by flow cytometry. Additionally, splenocytes of CD4 Δ Il7ra mice were stimulated with MOG 35 − 55 to assess their proliferative response and cytokine production by T helper cells. Results Loss of IL-7Rα from the surface of CD4 + T cells in CD4 Δ Il7ra mice was virtually complete several days after tamoxifen treatment. The loss of IL-7Rα in CD4 + T cells led to a gradual and substantial decrease in their numbers in both non-immunized and immunized CD4 Δ Il7ra mice, followed by slow repopulation up to the initial numbers. CD4 Δ Il7ra mice did not develop EAE. We found a decrease in the total numbers of TNF-, IFN-γ-, IL-17 A-, and GM-CSF-producing CD4 + T cells and regulatory T cells in the spleens and CNS of immunized CD4 Δ Il7ra mice. Tracking MOG 35 − 55 -specific CD4 + T cells revealed a significant reduction in their numbers in CD4 Δ Il7ra mice and decreased proliferation and cytokine production in response to MOG 35 − 55 . Conclusion Our study demonstrates that IL-7Rα on peripheral CD4 + T cells is essential for their maintenance, immune response, and EAE pathogenesis.","journal":"Journal of Neuroinflammation","year":2024,"id":437315,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":619049,"name":"Bram van den Broek","orcid":"0000-0003-1037-907X","position":1,"is_corresponding":false},{"id":281016,"name":"Larissa Lumi Watanabe Ishikawa","orcid":"0000-0003-3481-2181","position":2,"is_corresponding":false},{"id":1246168,"name":"Hamed Naziri","orcid":"0000-0001-6290-8944","position":3,"is_corresponding":false},{"id":1246169,"name":"Reza Yazdani","orcid":"0000-0002-3760-4137","position":4,"is_corresponding":false},{"id":281022,"name":"Guang‐Xian Zhang","orcid":"0000-0003-0017-5997","position":5,"is_corresponding":false},{"id":281023,"name":"Bogoljub Ćirić","orcid":"0000-0001-5361-7635","position":6,"is_corresponding":false},{"id":281024,"name":"Abdolmohamad Rostami","orcid":"0000-0003-0716-2726","position":7,"is_corresponding":false},{"id":884884,"name":"Gholamreza Azizi","orcid":"0000-0001-5658-2511","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:00:29.872940Z","pmid":"39380064","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":[]}