{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:53Z","timestamp":1785410573883,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,26]]},"group-title":"Immunology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM145290"],"award-info":[{"award-number":["R35GM145290"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R21AI168668"],"award-info":[{"award-number":["R21AI168668"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Allograft inflammatory factor-1 (AIF1) is a scaffold protein expressed predominantly in myeloid antigen-presenting cells (APCs) and associated with inflammatory disease. Although genetic studies have linked AIF1 loci to immune traits, its causal role in physiological immune responses remains poorly defined. We examined AIF1 deficiency using a conditional knockout model with deletion of AIF1 in hematopoietic cells (AIF1-cKO) during development and challenged mice with Listeria monocytogenes. AIF1 loss impaired bacterial clearance and diminished inflammatory responses, indicating reduced immune readiness during infection. AIF1-cKO mice exhibited impaired expansion of antigen-specific CD4+ and CD8+ T cells, accompanied by regulatory-associated phenotypic changes. These defects were associated with reduced cDC1 frequencies and transcriptional and phenotypic remodeling of splenic macrophages toward a less inflammatory state. Single-cell RNA sequencing revealed transcriptional alterations across multiple myeloid and lymphoid compartments despite AIF1 expression being largely restricted to myeloid APC, indicating broader immune remodeling. Increased Tgfbr1 expression was a recurrent feature across several immune populations. Consistent with this finding, AIF1-deficient cells displayed enhanced TGF\u03b2 responsiveness, while Tgfbr1 silencing partially restored inflammatory responses and T cell priming\n                  <jats:italic>ex vivo<\/jats:italic>\n                  . These findings establish AIF1 as a regulator of immune competence that promotes effective innate and adaptive immune responses.\n                <\/jats:p>","DOI":"10.64898\/2026.07.23.739600","type":"posted-content","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:34:32Z","timestamp":1785130472000},"source":"Crossref","is-referenced-by-count":0,"title":["Allograft Inflammatory Factor-1 regulates immune activation states and is required for effective pathogen-specific T cell immunity during infection"],"prefix":"10.64898","author":[{"given":"Lais","family":"Rekowsky","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Louzada","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis MN, USA"},{"name":"Department of Biology, Federal University of Sergipe, Aracaju, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayane","family":"Resende","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Seenarine","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Macchietto","sequence":"additional","affiliation":[{"name":"University of Minnesota Supercomputing Institute, University of Minnesota, Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"de Moura","sequence":"additional","affiliation":[{"name":"Department of Morphology, Federal University of Sergipe, S\u00e3o Crist\u00f3v\u00e3o, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Elizondo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2644-0529","authenticated-orcid":false,"given":"Michael W.","family":"Lipscomb","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis MN, USA"},{"name":"Center for Immunology, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072819500502000_2026.07.23.739600v1.1","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/dvg.22424","article-title":"Genetic inactivation of the allograft inflammatory factor-1 locus","volume":"51","year":"2013","journal-title":"Genesis"},{"key":"2026072819500502000_2026.07.23.739600v1.2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.1612"},{"key":"2026072819500502000_2026.07.23.739600v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.09.027"},{"key":"2026072819500502000_2026.07.23.739600v1.4","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2001.01301.x"},{"key":"2026072819500502000_2026.07.23.739600v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199810)24:2<244::AID-GLIA9>3.0.CO;2-3"},{"key":"2026072819500502000_2026.07.23.739600v1.6","first-page":"1387","article-title":"Allograft inflammatory factory-1","volume":"61","year":"1996","journal-title":"A cytokine-responsive macrophage molecule expressed in transplanted human hearts. Transplantation"},{"key":"2026072819500502000_2026.07.23.739600v1.7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118003"},{"key":"2026072819500502000_2026.07.23.739600v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh316"},{"key":"2026072819500502000_2026.07.23.739600v1.9","doi-asserted-by":"publisher","DOI":"10.1007\/s004010000233"},{"key":"2026072819500502000_2026.07.23.739600v1.10","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5388"},{"key":"2026072819500502000_2026.07.23.739600v1.11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00381.2005"},{"key":"2026072819500502000_2026.07.23.739600v1.12","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000074000.03562.CC"},{"key":"2026072819500502000_2026.07.23.739600v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn242"},{"key":"2026072819500502000_2026.07.23.739600v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(98)00040-0"},{"key":"2026072819500502000_2026.07.23.739600v1.15","first-page":"181","article-title":"Allograft inflammatory factor-1 augments macrophage phagocytotic activity and accelerates the progression of atherosclerosis in ApoE-\/-mice","volume":"21","year":"2008","journal-title":"Int J Mol Med"},{"key":"2026072819500502000_2026.07.23.739600v1.16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01502"},{"key":"2026072819500502000_2026.07.23.739600v1.17","doi-asserted-by":"crossref","unstructured":"Elizondo DM , Brandy NZD , da Silva RLL , Haddock NL , Kacsinta AD , de Moura TR , Lipscomb MW . Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro. Frontiers in Immunology 2019; 10.","DOI":"10.3389\/fimmu.2019.00173"},{"key":"2026072819500502000_2026.07.23.739600v1.18","doi-asserted-by":"crossref","first-page":"e95859","DOI":"10.1371\/journal.pone.0095859","article-title":"allograft inflammatory factor 1 functions as a pro-inflammatory cytokine in the oyster, Crassostrea ariakensis","volume":"9","year":"2014","journal-title":"PLoS One"},{"key":"2026072819500502000_2026.07.23.739600v1.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1814705115"},{"key":"2026072819500502000_2026.07.23.739600v1.20","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken376"},{"key":"2026072819500502000_2026.07.23.739600v1.21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.5.3316"},{"key":"2026072819500502000_2026.07.23.739600v1.22","doi-asserted-by":"crossref","unstructured":"Elizondo DM , Brandy NZ , da Silva RL , de Moura TR , Lipscomb MW . Allograft inflammatory factor-1 in myeloid cells drives autoimmunity in type 1 diabetes. JCI Insight 2020; 5.","DOI":"10.1172\/jci.insight.136092"},{"key":"2026072819500502000_2026.07.23.739600v1.23","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1002\/mus.21033","article-title":"Allograft inflammatory factor-1: a pathogenetic factor for vasculitic neuropathy","volume":"38","year":"2008","journal-title":"Muscle Nerve"},{"key":"2026072819500502000_2026.07.23.739600v1.24","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kem057"},{"key":"2026072819500502000_2026.07.23.739600v1.25","doi-asserted-by":"crossref","first-page":"233","DOI":"10.2119\/molmed.2014.00264","article-title":"Loss of Allograft Inflammatory Factor-1 Ameliorates Experimental Autoimmune Encephalomyelitis by Limiting Encephalitogenic CD4 T-Cell Expansion","volume":"21","year":"2015","journal-title":"Mol Med"},{"key":"2026072819500502000_2026.07.23.739600v1.26","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2003.01714.x"},{"key":"2026072819500502000_2026.07.23.739600v1.27","doi-asserted-by":"crossref","first-page":"e94","DOI":"10.1093\/jpids\/pix025","article-title":"Allograft Inflammatory Factor-1 Links T-Cell Activation, Interferon Response, and Macrophage Activation in Chronic Kawasaki Disease Arteritis","volume":"6","year":"2017","journal-title":"J Pediatric Infect Dis Soc"},{"key":"2026072819500502000_2026.07.23.739600v1.28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2004.00621.x"},{"key":"2026072819500502000_2026.07.23.739600v1.29","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1016\/j.transproceed.2010.09.091","article-title":"Cardiac allograft rejection correlates with increased expressions of Toll-like receptors 2 and 4 and allograft inflammatory factor 1","volume":"42","year":"2010","journal-title":"Transplant Proc"},{"key":"2026072819500502000_2026.07.23.739600v1.30","doi-asserted-by":"crossref","unstructured":"Piotrowska K , Sluczanowska-Glabowska S , Kurzawski M , Dziedziejko V , Kopytko P , Paczkowska E , et al. Over-Expression of Allograft Inflammatory Factor-1 (AIF-1) in Patients with Rheumatoid Arthritis. Biomolecules 2020; 10.","DOI":"10.3390\/biom10071064"},{"key":"2026072819500502000_2026.07.23.739600v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(02)00799-1"},{"key":"2026072819500502000_2026.07.23.739600v1.32","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/j.1399-0039.2007.00830.x","article-title":"Allograft inflammatory factor-1 and tumor necrosis factor single nucleotide polymorphisms in systemic sclerosis","volume":"69","year":"2007","journal-title":"Tissue Antigens"},{"key":"2026072819500502000_2026.07.23.739600v1.33","doi-asserted-by":"crossref","first-page":"506","DOI":"10.12659\/AOT.893885","article-title":"Influence of AIF1 Gene Polymorphisms on Long-Term Kidney Allograft Function","volume":"20","year":"2015","journal-title":"Ann Transplant"},{"key":"2026072819500502000_2026.07.23.739600v1.34","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.humimm.2015.11.008","article-title":"Expression of allograft inflammatory factor-1 in peripheral blood monocytes and synovial membranes in patients with rheumatoid arthritis","volume":"77","year":"2016","journal-title":"Hum Immunol"},{"key":"2026072819500502000_2026.07.23.739600v1.35","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1089\/gtmb.2011.0201","article-title":"Allograft inflammatory factor-1 gene polymorphisms in patients with rheumatoid arthritis","volume":"16","year":"2012","journal-title":"Genet Test Mol Biomarkers"},{"key":"2026072819500502000_2026.07.23.739600v1.36","doi-asserted-by":"crossref","unstructured":"Antonello PC , Hodgkinson CA , Feng D , Marietta C , Mohana Krishnan B , Parra MA , et al. Genetic regulation of AIF1 shapes immune and liver injury profiles in chronic alcohol use. JCI Insight 2026; 11.","DOI":"10.1172\/jci.insight.198209"},{"key":"2026072819500502000_2026.07.23.739600v1.37","doi-asserted-by":"crossref","unstructured":"Elizondo DM , Andargie TE , Haddock NL , da Silva RLL , de Moura TR , Lipscomb MW . IL-10 producing CD8(+) CD122(+) PD-1(+) regulatory T cells are expanded by dendritic cells silenced for Allograft Inflammatory Factor-1. J Leukoc Biol 2018.","DOI":"10.1002\/JLB.1A0118-010RR"},{"key":"2026072819500502000_2026.07.23.739600v1.38","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00334.2006"},{"key":"2026072819500502000_2026.07.23.739600v1.39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200935200"},{"key":"2026072819500502000_2026.07.23.739600v1.40","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.17.3073"},{"key":"2026072819500502000_2026.07.23.739600v1.41","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.bbrc.2022.04.089","article-title":"Allograft inflammatory factor-1 enhances inflammation and oxidative stress via the NF-kappaB pathway in diabetic kidney disease","volume":"614","year":"2022","journal-title":"Biochem Biophys Res Commun"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.23.739600","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T02:50:14Z","timestamp":1785293414000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.07.23.739600"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,26]]},"references-count":41,"URL":"https:\/\/doi.org\/10.64898\/2026.07.23.739600","relation":{},"subject":[],"published":{"date-parts":[[2026,7,26]]},"subtype":"preprint"}}