{"doi":"10.1172/jci150143","title":"Inherited human c-Rel deficiency disrupts myeloid and lymphoid immunity to multiple infectious agents","abstract":"We studied a child with severe viral, bacterial, fungal, and parasitic diseases, who was homozygous for a loss-of-function mutation of REL, encoding c-Rel, which is selectively expressed in lymphoid and myeloid cells. The patient had low frequencies of NK, effector memory cells reexpressing CD45RA (Temra) CD8+ T cells, memory CD4+ T cells, including Th1 and Th1*, Tregs, and memory B cells, whereas the counts and proportions of other leukocyte subsets were normal. Functional deficits of myeloid cells included the abolition of IL-12 and IL-23 production by conventional DC1s (cDC1s) and monocytes, but not cDC2s. c-Rel was also required for induction of CD86 expression on, and thus antigen-presenting cell function of, cDCs. Functional deficits of lymphoid cells included reduced IL-2 production by naive T cells, correlating with low proliferation and survival rates and poor production of Th1, Th2, and Th17 cytokines by memory CD4+ T cells. In naive CD4+ T cells, c-Rel is dispensable for early IL2 induction but contributes to later phases of IL2 expression. The patient's naive B cells displayed impaired MYC and BCL2L1 induction, compromising B cell survival and proliferation and preventing their differentiation into Ig-secreting plasmablasts. Inherited c-Rel deficiency disrupts the development and function of multiple myeloid and lymphoid cells, compromising innate and adaptive immunity to multiple infectious agents.","journal":"Journal of Clinical Investigation","year":2021,"id":160200,"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":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":558864,"name":"David Langlais","orcid":"0000-0003-4429-0110","position":1,"is_corresponding":false},{"id":104147,"name":"Vivien Béziat","orcid":"0000-0002-4020-824X","position":2,"is_corresponding":false},{"id":104485,"name":"Franck Rapaport","orcid":"0000-0001-6553-2110","position":3,"is_corresponding":false},{"id":281881,"name":"Geetha Rao","orcid":"0009-0007-2744-9309","position":4,"is_corresponding":false},{"id":672529,"name":"Tomi Lazarov","orcid":"0000-0002-6312-0080","position":5,"is_corresponding":false},{"id":550822,"name":"Mathieu Bourgey","orcid":"0000-0002-8432-834X","position":6,"is_corresponding":false},{"id":664790,"name":"Yu Zhou","orcid":"0000-0001-5594-2167","position":7,"is_corresponding":false},{"id":673238,"name":"Coralie Briand","orcid":null,"position":8,"is_corresponding":false},{"id":670958,"name":"Kunihiko Moriya","orcid":"0000-0002-0418-5132","position":9,"is_corresponding":false},{"id":270308,"name":"Fatima Ailal","orcid":"0000-0001-5824-3193","position":10,"is_corresponding":false},{"id":673239,"name":"Danielle T. 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