{"doi":"10.1002/art.42146","title":"Interleukin‐13 Receptor α1–Mediated Signaling Regulates <scp>Age‐Associated</scp>/Autoimmune B Cell Expansion and Lupus Pathogenesis","abstract":"OBJECTIVE: Age-associated/autoimmune B cells (ABCs) are an emerging B cell subset with aberrant expansion in systemic lupus erythematosus. ABC generation and differentiation exhibit marked sexual dimorphism, and Toll-like receptor 7 (TLR-7) engagement is a key contributor to these sex differences. ABC generation is also controlled by interleukin-21 (IL-21) and its interplay with interferon-γ and IL-4. This study was undertaken to investigate whether IL-13 receptor α1 (IL-13Rα1), an X-linked receptor that transmits IL-4/IL-13 signals, regulates ABCs and lupus pathogenesis. METHODS: Mice lacking DEF-6 and switch-associated protein 70 (double-knockout [DKO]), which preferentially develop lupus in females, were crossed with IL-13Rα1-knockout mice. IL-13Rα1-knockout male mice were also crossed with Y chromosome autoimmune accelerator (Yaa) DKO mice, which overexpress TLR-7 and develop severe disease. ABCs were assessed using flow cytometry and RNA-Seq. Lupus pathogenesis was evaluated using serologic and histologic analyses. RESULTS: ABCs expressed higher levels of IL-13Rα1 than follicular B cells. The absence of IL-13Rα1 in either DKO female mice or Yaa DKO male mice decreased the accumulation of ABCs, the differentiation of ABCs into plasmablasts, and autoantibody production. Lack of IL-13Rα1 also prolonged survival and delayed the development of tissue inflammation. IL-13Rα1 deficiency diminished in vitro generation of ABCs, an effect that, surprisingly, could be observed in response to IL-21 alone. RNA-Seq revealed that ABCs lacking IL-13Rα1 down-regulated some histologic characteristics of B cells but up-regulated myeloid markers and proinflammatory mediators. CONCLUSION: Our findings indicate a novel role for IL-13Rα1 in controlling ABC generation and differentiation, suggesting that IL-13Rα1 contributes to these effects by regulating a subset of IL-21-mediated signaling events. These results also suggest that X-linked genes besides TLR7 participate in the regulation of ABCs in lupus.","journal":"Arthritis & Rheumatology","year":2022,"id":269561,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9656,"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":853328,"name":"Danny Flores Castro","orcid":"0000-0001-8263-9104","position":1,"is_corresponding":false},{"id":420515,"name":"Sanjay Gupta","orcid":"0000-0003-1714-3895","position":2,"is_corresponding":false},{"id":853327,"name":"Swati Phalke","orcid":"0000-0002-9061-0931","position":3,"is_corresponding":false},{"id":420517,"name":"Michela Manni","orcid":"0000-0002-8916-1788","position":4,"is_corresponding":false},{"id":506354,"name":"Juan Rivera‐Correa","orcid":"0000-0003-4822-0005","position":5,"is_corresponding":false},{"id":634536,"name":"Rolf Jessberger","orcid":"0000-0002-2972-2192","position":6,"is_corresponding":false},{"id":825650,"name":"Habib Zaghouani","orcid":"0000-0003-4653-0050","position":7,"is_corresponding":false},{"id":647232,"name":"Ευγενία Γιαννοπούλου","orcid":null,"position":8,"is_corresponding":false},{"id":383407,"name":"Tania Pannellini","orcid":"0000-0002-0224-9921","position":9,"is_corresponding":false},{"id":420518,"name":"Alessandra B. Pernis","orcid":"0000-0001-8259-1446","position":10,"is_corresponding":false},{"id":932744,"name":"Zhu Chen","orcid":"0000-0003-0828-1583","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T00:27:22.602796Z","pmid":"35438841","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":[]}