{"doi":"10.1093/immhor/vlaf063","title":"Type I interferon production in myeloid cells is regulated by factors independent of <i>Ptpn22</i>","abstract":"The immune regulatory gene PTPN22 is expressed in all immune cells and encodes lymphoid protein (Lyp) in humans and the ortholog PEST domain-enriched phosphatase (PEP) in mice. The PTPN22 alternative allele, 1858C>T, is expressed in 5% to 15% of the North American population and is strongly associated with the development of autoimmune disease while simultaneously capable of providing protection during viral infection and cancer. In murine models, significant progress has been made in elucidating the molecular mechanisms by which PEP and its pro-autoimmune variant (PEP-R619W) modulate T-cell function, yet their influence on non-T-cell pathways, such as antigen-presenting cell cytokine production, remains less defined. Previously, it was reported that PEP promotes type I interferon (IFN-I) production in dendritic cells (DCs) and macrophages following TLR4 stimulus. Here, we show that contrary to previous results, PEP and the PEP-R619W variant do not mediate IFN-I production in DCs and macrophages following exposure to LPS, 3p-hpRNA, or coronavirus mouse hepatitis virus strain A59. We attribute the prior findings to mouse strain-specific differences and conclude that factors independent of PEP may be regulating IFN-I production in these studies. We further show that PEP and its R619W variant distinctly modulate the production of TNF-α, IL-12, and IL-2 in DCs following LPS stimulus. Taken together, our results challenge the current understanding of the role of PEP during inflammation while providing new insight into how the PEP-R619W variant may alter myeloid cell function during disease.","journal":"ImmunoHorizons","year":2025,"id":535382,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1276817,"name":"Anam Fatima Shaikh","orcid":null,"position":1,"is_corresponding":false},{"id":1419487,"name":"Alec M Bevis","orcid":null,"position":2,"is_corresponding":false},{"id":1419488,"name":"Tammy R Cockerham","orcid":null,"position":3,"is_corresponding":false},{"id":420496,"name":"Robin C. Orozco","orcid":"0000-0002-2138-2912","position":4,"is_corresponding":false},{"id":392557,"name":"Jenna Barnes","orcid":"0000-0001-5153-553X","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41208109","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":[]}