{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:13:39Z","timestamp":1789629219392,"version":"build-2803163510"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CCR5 is a potent mediator of regulatory T cell (Treg) chemotaxis. In murine histoplasmosis, mice lacking CCR5 or endogenous CCL4 have a reduced number of Tregs in the lungs, which results in accelerated resolution of infection. In this study, we demonstrate that CCR5 controls the outcome of Histoplasma capsulatum infection by dictating thymic and lymph node egress of Tregs. Mice lacking CCR5 or treated with a mAb to CCL4 had more Tregs in the thymus prior to and during infection. Thymic accumulation was associated with diminished transcription of the sphingosine 1-phosphate 1 receptor and Kr\u00fcppel-like factor 2, both of which regulate thymic and lymph node emigration of T cells. The significance of CCR5 in Treg egress was demonstrated by generating mixed bone marrow chimeras. Chimeric mice had an increased proportion of CCR5\u2212\/\u2212 Tregs in the thymus and lymph nodes and a decreased proportion of Tregs in the lungs prior to and during H. capsulatum infection. Hence, CCR5 signaling regulates pathogen persistence in murine histoplasmosis by regulating Tregs exiting from the thymus and lymph nodes and, consequently, their subsequent homing in the periphery.<\/jats:p>","DOI":"10.4049\/jimmunol.1003876","type":"journal-article","created":{"date-parts":[[2011,4,9]],"date-time":"2011-04-09T02:52:07Z","timestamp":1302317527000},"page":"5949-5955","source":"Crossref","is-referenced-by-count":24,"title":["An Aberrant Thymus in CCR5\u2212\/\u2212 Mice Is Coupled with an Enhanced Adaptive Immune Response in Fungal Infection"],"prefix":"10.1093","volume":"186","author":[{"given":"Danielle N","family":"Kroetz","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine , Cincinnati, OH 45267"},{"name":"Division of Infectious Diseases, University of Cincinnati College of Medicine , Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"George S","family":"Deepe","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine , Cincinnati, OH 45267"},{"name":"Division of Infectious Diseases, University of Cincinnati College of Medicine , Cincinnati, OH 45267"},{"name":"Veterans Affairs Hospital , Cincinnati, OH 45220"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,5,15]]},"reference":[{"key":"2025032411262059600_r1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/ni904","article-title":"Foxp3 programs the development and function of CD4+CD25+ regulatory T cells","volume":"4","author":"Fontenot","year":"2003","journal-title":"Nat. Immunol."},{"key":"2025032411262059600_r2","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1126\/science.1079490","article-title":"Control of regulatory T cell development by the transcription factor Foxp3","volume":"299","author":"Hori","year":"2003","journal-title":"Science"},{"key":"2025032411262059600_r3","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.micinf.2004.02.020","article-title":"Foxp3: a critical regulator of the development and function of regulatory T cells","volume":"6","author":"Hori","year":"2004","journal-title":"Microbes Infect."},{"key":"2025032411262059600_r4","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.4049\/jimmunol.180.5.3049","article-title":"CCR5-dependent regulatory T cell migration mediates fungal survival and severe immunosuppression","volume":"180","author":"Moreira","year":"2008","journal-title":"J. Immunol."},{"key":"2025032411262059600_r5","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1084\/jem.20060956","article-title":"CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of Leishmania major infection favors pathogen persistence","volume":"203","author":"Yurchenko","year":"2006","journal-title":"J. Exp. Med."},{"key":"2025032411262059600_r6","doi-asserted-by":"crossref","first-page":"5224","DOI":"10.4049\/jimmunol.1000032","article-title":"CCR5 dictates the equilibrium of proinflammatory IL-17+ and regulatory Foxp3+ T cells in fungal infection","volume":"184","author":"Kroetz","year":"2010","journal-title":"J. Immunol."},{"key":"2025032411262059600_r7","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.4049\/jimmunol.180.2.1088","article-title":"TNF-\u03b1 antagonism generates a population of antigen-specific CD4+CD25+ T cells that inhibit protective immunity in murine histoplasmosis","volume":"180","author":"Deepe","year":"2008","journal-title":"J. Immunol."},{"key":"2025032411262059600_r8","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1172\/JCI25365","article-title":"Apoptosis modulates protective immunity to the pathogenic fungus Histoplasma capsulatum","volume":"115","author":"Allen","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2025032411262059600_r9","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1046\/j.1365-2567.1999.00816.x","article-title":"Phenotypic identification of the subgroups of murine T-cell receptor alphabeta+ CD4+ CD8- thymocytes and its implication in the late stage of thymocyte development","volume":"97","author":"Ge","year":"1999","journal-title":"Immunology"},{"key":"2025032411262059600_r10","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/intimm\/13.3.313","article-title":"Heterogeneity within medullary-type TCRalphabeta(+)CD3(+)CD4(-)CD8(+) thymocytes in normal mouse thymus","volume":"13","author":"Tian","year":"2001","journal-title":"Int. Immunol."},{"key":"2025032411262059600_r11","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1126\/science.1070238","article-title":"Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists","volume":"296","author":"Mandala","year":"2002","journal-title":"Science"},{"key":"2025032411262059600_r12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature02284","article-title":"Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1","volume":"427","author":"Matloubian","year":"2004","journal-title":"Nature"},{"key":"2025032411262059600_r13","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/ni1565","article-title":"Transcription factor KLF2 regulates the migration of naive T cells by restricting chemokine receptor expression patterns","volume":"9","author":"Sebzda","year":"2008","journal-title":"Nat. Immunol."},{"key":"2025032411262059600_r14","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1172\/JCI41384","article-title":"Statin-induced Kr\u00fcppel-like factor 2 expression in human and mouse T cells reduces inflammatory and pathogenic responses","volume":"120","author":"Bu","year":"2010","journal-title":"J. Clin. Invest."},{"key":"2025032411262059600_r15","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.4049\/jimmunol.174.3.1230","article-title":"Phosphatidylinositol 3-kinase regulates thymic exit","volume":"174","author":"Barbee","year":"2005","journal-title":"J. Immunol."},{"key":"2025032411262059600_r16","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1128\/iai.37.3.940-945.1982","article-title":"Immunoregulation in disseminated histoplasmosis: characterization of the surface phenotype of splenic suppressor T lymphocytes","volume":"37","author":"Watson","year":"1982","journal-title":"Infect. Immun."},{"key":"2025032411262059600_r17","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ni1178","article-title":"Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self","volume":"6","author":"Sakaguchi","year":"2005","journal-title":"Nat. Immunol."},{"key":"2025032411262059600_r18","doi-asserted-by":"crossref","first-page":"7973","DOI":"10.4049\/jimmunol.175.12.7973","article-title":"The sphingosine 1-phosphate receptor agonist FTY720 differentially affects the sequestration of CD4+\/CD25+ T-regulatory cells and enhances their functional activity","volume":"175","author":"Sawicka","year":"2005","journal-title":"J. Immunol."},{"key":"2025032411262059600_r19","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/ni.1743","article-title":"The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR","volume":"10","author":"Liu","year":"2009","journal-title":"Nat. Immunol."},{"key":"2025032411262059600_r20","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.4049\/jimmunol.182.3.1746","article-title":"Disruption of CCR5-dependent homing of regulatory T cells inhibits tumor growth in a murine model of pancreatic cancer","volume":"182","author":"Tan","year":"2009","journal-title":"J. Immunol."},{"key":"2025032411262059600_r21","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/ni735","article-title":"B cells and professional APCs recruit regulatory T cells via CCL4","volume":"2","author":"Bystry","year":"2001","journal-title":"Nat. Immunol."},{"key":"2025032411262059600_r22","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1182\/blood.V91.8.2905.2905_2905_2913","article-title":"Macrophage inflammatory protein-1\u03b2 induces migration and activation of human thymocytes","volume":"91","author":"Dairaghi","year":"1998","journal-title":"Blood"},{"key":"2025032411262059600_r23","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/ni.1731","article-title":"The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation","volume":"10","author":"Koch","year":"2009","journal-title":"Nat. Immunol."},{"key":"2025032411262059600_r24","doi-asserted-by":"crossref","first-page":"15396","DOI":"10.1074\/jbc.M314291200","article-title":"Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration","volume":"279","author":"Allende","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2025032411262059600_r25","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nature04882","article-title":"Kruppel-like factor 2 regulates thymocyte and T-cell migration","volume":"442","author":"Carlson","year":"2006","journal-title":"Nature"},{"key":"2025032411262059600_r26","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.4049\/jimmunol.161.6.3103","article-title":"CXCR4 and CCR5 on human thymocytes: biological function and role in HIV-1 infection","volume":"161","author":"Zaitseva","year":"1998","journal-title":"J. Immunol."},{"key":"2025032411262059600_r27","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S1074-7613(02)00267-4","article-title":"Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus","volume":"16","author":"Ueno","year":"2002","journal-title":"Immunity"},{"key":"2025032411262059600_r28","doi-asserted-by":"crossref","first-page":"855","DOI":"10.4049\/jimmunol.173.2.855","article-title":"FTY720-enhanced T cell homing is dependent on CCR2, CCR5, CCR7, and CXCR4: evidence for distinct chemokine compartments","volume":"173","author":"Yopp","year":"2004","journal-title":"J. Immunol."},{"key":"2025032411262059600_r29","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nature01158","article-title":"The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease","volume":"420","author":"Youssef","year":"2002","journal-title":"Nature"},{"key":"2025032411262059600_r30","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1161\/01.RES.0000101298.76864.14","article-title":"Inhibition of hydroxymethylglutaryl-coenzyme a reductase reduces Th1 development and promotes Th2 development","volume":"93","author":"Hakamada-Taguchi","year":"2003","journal-title":"Circ. Res."},{"key":"2025032411262059600_r31","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.atherosclerosis.2007.07.031","article-title":"The effect of HMG-CoA reductase inhibitors on naturally occurring CD4+CD25+ T cells","volume":"197","author":"Mausner-Fainberg","year":"2008","journal-title":"Atherosclerosis"},{"key":"2025032411262059600_r32","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev.immunol.21.090501.080131","article-title":"Ligands for L-selectin: homing, inflammation, and beyond","volume":"22","author":"Rosen","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"2025032411262059600_r33","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev.immunol.22.012703.104649","article-title":"Integrins and T cell-mediated immunity","volume":"22","author":"Pribila","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"2025032411262059600_r34","doi-asserted-by":"crossref","first-page":"7632","DOI":"10.4049\/jimmunol.178.12.7632","article-title":"Kruppel-like factor 2 controls T cell trafficking by activating L-selectin (CD62L) and sphingosine-1-phosphate receptor 1 transcription","volume":"178","author":"Bai","year":"2007","journal-title":"J. Immunol."},{"key":"2025032411262059600_r35","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1084\/jem.20071477","article-title":"The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells","volume":"205","author":"Haxhinasto","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025032411262059600_r36","doi-asserted-by":"crossref","first-page":"7797","DOI":"10.1073\/pnas.0800928105","article-title":"T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR","volume":"105","author":"Sauer","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032411262059600_r37","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1182\/blood-2009-08-237784","article-title":"CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus","volume":"115","author":"Zlotoff","year":"2010","journal-title":"Blood"},{"key":"2025032411262059600_r38","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1084\/jem.20040643","article-title":"CCR7 signals are essential for cortex-medulla migration of developing thymocytes","volume":"200","author":"Ueno","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025032411262059600_r39","doi-asserted-by":"crossref","first-page":"3999","DOI":"10.4049\/jimmunol.172.7.3999","article-title":"CCR7 directs the migration of thymocytes into the thymic medulla","volume":"172","author":"Kwan","year":"2004","journal-title":"J. Immunol."},{"key":"2025032411262059600_r40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.immuni.2005.12.011","article-title":"CCR7-dependent cortex-to-medulla migration of positively selected thymocytes is essential for establishing central tolerance","volume":"24","author":"Kurobe","year":"2006","journal-title":"Immunity"},{"key":"2025032411262059600_r41","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.immuni.2009.09.020","article-title":"Differential contribution of chemotaxis and substrate restriction to segregation of immature and mature thymocytes","volume":"31","author":"Ehrlich","year":"2009","journal-title":"Immunity"},{"key":"2025032411262059600_r42","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4049\/jimmunol.182.1.171","article-title":"CCR5 expression levels influence NFAT translocation, IL-2 production, and subsequent signaling events during T lymphocyte activation","volume":"182","author":"Camargo","year":"2009","journal-title":"J. Immunol."},{"key":"2025032411262059600_r43","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1146\/annurev.immunol.26.021607.090357","article-title":"The biology of interleukin-2","volume":"26","author":"Malek","year":"2008","journal-title":"Annu. Rev. Immunol."},{"key":"2025032411262059600_r44","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/ni.1995","article-title":"Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5","volume":"12","author":"Yang","year":"2011","journal-title":"Nat. Immunol."},{"key":"2025032411262059600_r45","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1084\/jem.20091885","article-title":"Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosis","volume":"207","author":"Shafiani","year":"2010","journal-title":"J. Exp. Med."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/186\/10\/5949\/62471814\/1003876.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/186\/10\/5949\/62471814\/1003876.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T17:11:20Z","timestamp":1743181880000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/186\/10\/5949\/7996663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5]]},"references-count":45,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2011,5,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1003876","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,5]]},"published":{"date-parts":[[2011,5]]}}}