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Using the epididymis, a model for studying tubular organs, we uncovered a novel and unexpected role for professional proton-secreting \u2018clear cells\u2019 in sperm maturation and immune defense. The epididymal epithelium participates in the maturation of spermatozoa via the establishment of an acidic milieu and transfer of proteins to sperm cells, a poorly characterized process. We show that proton-secreting clear cells express mRNA transcripts and proteins that are acquired by maturing sperm, and that they establish close interactions with luminal spermatozoa via newly described \u2018nanotubes\u2019. Mechanistic studies show that injection of bacterial antigens in vivo induces chemokine expression in clear cells, followed by macrophage recruitment into the organ. Injection of an inflammatory intermediate mediator (IFN-\u03b3) increased Cxcl10 expression in clear cells, revealing their participation as sensors and mediators of inflammation. The functional diversity adopted by clear cells might represent a generalized phenomenon by which similar epithelial cells decode signals, communicate with neighbors and mediate mucosal immunity, depending on their precise location within an organ.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/jcs.233239","type":"journal-article","created":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T15:27:39Z","timestamp":1571671659000},"source":"Crossref","is-referenced-by-count":43,"title":["Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity"],"prefix":"10.1242","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0490-9548","authenticated-orcid":false,"given":"Maria A.","family":"Battistone","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School 1 Program in Membrane Biology, Center for Systems Biology and Nephrology Division, Department of Medicine , , Boston, MA 02114 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5402-3687","authenticated-orcid":false,"given":"Raul German","family":"Spallanzani","sequence":"additional","affiliation":[{"name":"Harvard Medical School, and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital 2 Division of Immunology, Department of Microbiology and Immunobiology , , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra C.","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School 1 Program in Membrane Biology, Center for Systems Biology and Nephrology Division, Department of Medicine , , Boston, MA 02114 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Capen","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School 1 Program in Membrane Biology, Center for Systems Biology and Nephrology Division, Department of Medicine , , Boston, MA 02114 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil V.","family":"Nair","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School 1 Program in Membrane Biology, Center for Systems Biology and Nephrology Division, Department of Medicine , , Boston, MA 02114 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Brown","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School 1 Program in Membrane Biology, Center for Systems Biology and Nephrology Division, Department of Medicine , , Boston, MA 02114 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6380-8689","authenticated-orcid":false,"given":"Sylvie","family":"Breton","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School 1 Program in Membrane Biology, Center for Systems Biology and Nephrology Division, Department of Medicine , , Boston, MA 02114 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,11,18]]},"reference":[{"key":"2024072613405810400_JCS233239C1","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1111\/j.1745-7262.2007.00280.x","article-title":"Proteomic changes in mammalian spermatozoa during epididymal maturation","volume":"9","author":"Aitken","year":"2007","journal-title":"Asian J. 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