{"doi":"10.4049/immunohorizons.2300016","title":"Serendipitous Discovery of T Cell–Produced KLK1b22 as a Regulator of Systemic Metabolism","abstract":"In order to study mechanistic/mammalian target of rapamycin's role in T cell differentiation, we generated mice in which Rheb is selectively deleted in T cells (T-Rheb-/- C57BL/6J background). During these studies, we noted that T-Rheb-/- mice were consistently heavier but had improved glucose tolerance and insulin sensitivity as well as a marked increase in beige fat. Microarray analysis of Rheb-/- T cells revealed a marked increase in expression of kallikrein 1-related peptidase b22 (Klk1b22). Overexpression of KLK1b22 in vitro enhanced insulin receptor signaling, and systemic overexpression of KLK1b22 in C57BL/6J mice also enhances glucose tolerance. Although KLK1B22 expression was markedly elevated in the T-Rheb-/- T cells, we never observed any expression in wild-type T cells. Interestingly, in querying the mouse Immunologic Genome Project, we found that Klk1b22 expression was also increased in wild-type 129S1/SVLMJ and C3HEJ mice. Indeed, both strains of mice demonstrate exceptionally improved glucose tolerance. This prompted us to employ CRISPR-mediated knockout of KLK1b22 in 129S1/SVLMJ mice, which in fact led to reduced glucose tolerance. Overall, our studies reveal (to our knowledge) a novel role for KLK1b22 in regulating systemic metabolism and demonstrate the ability of T cell-derived KLK1b22 to regulate systemic metabolism. Notably, however, further studies have revealed that this is a serendipitous finding unrelated to Rheb.","journal":"ImmunoHorizons","year":2023,"id":377137,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":228361,"name":"Im‐Hong Sun","orcid":"0000-0003-0288-2062","position":1,"is_corresponding":false},{"id":229834,"name":"Chirag H. Patel","orcid":null,"position":2,"is_corresponding":false},{"id":229833,"name":"Im-Meng Sun","orcid":null,"position":3,"is_corresponding":false},{"id":228360,"name":"Min Hee Oh","orcid":"0000-0003-1581-4288","position":4,"is_corresponding":false},{"id":698526,"name":"Ian A. Bettencourt","orcid":"0000-0001-8154-7670","position":5,"is_corresponding":false},{"id":831903,"name":"Michael D. Claiborne","orcid":"0000-0002-7633-0159","position":6,"is_corresponding":false},{"id":229835,"name":"Yee Chan‐Li","orcid":null,"position":7,"is_corresponding":false},{"id":228362,"name":"Liang Zhao","orcid":"0000-0002-2126-6778","position":8,"is_corresponding":false},{"id":471554,"name":"Adam T. Waickman","orcid":"0000-0002-4536-6714","position":9,"is_corresponding":false},{"id":896249,"name":"Orestes Mavrothalassitis","orcid":"0000-0002-2301-9682","position":10,"is_corresponding":false},{"id":41931,"name":"Jiayu Wen","orcid":"0000-0003-1249-6456","position":11,"is_corresponding":false},{"id":690273,"name":"Susan Aja","orcid":null,"position":12,"is_corresponding":false},{"id":228375,"name":"Jonathan D. Powell","orcid":"0000-0002-0850-2852","position":13,"is_corresponding":false},{"id":228369,"name":"Matthew L. Arwood","orcid":"0000-0003-4737-9786","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:16:36.370283Z","pmid":"37358498","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":[]}