{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:12:56Z","timestamp":1792725176835,"version":"4.5.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"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":[[2016,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Short-chain fatty acids (SCFAs) are major products of gut microbial fermentation and profoundly affect host health and disease. SCFAs generate IL-10+ regulatory T cells, which may promote immune tolerance. However, SCFAs can also induce Th1 and Th17 cells upon immunological challenges and, therefore, also have the potential to induce inflammatory responses. Because of the seemingly paradoxical SCFA activities in regulating T cells, we investigated, in depth, the impact of elevated SCFA levels on T cells and tissue inflammation in mice. Orally administered SCFAs induced effector (Th1 and Th17) and regulatory T cells in ureter and kidney tissues, and they induced T cell\u2013mediated ureteritis, leading to kidney hydronephrosis (hereafter called acetate-induced renal disease, or C2RD). Kidney hydronephrosis in C2RD was caused by ureteral obstruction, which was, in turn, induced by SCFA-induced inflammation in the ureteropelvic junction and proximal ureter. Oral administration of all major SCFAs, such as acetate, propionate, and butyrate, induced the disease. We found that C2RD development is dependent on mammalian target of rapamycin activation, T cell\u2013derived inflammatory cytokines such as IFN-\u03b3 and IL-17, and gut microbiota. Young or male animals were more susceptible than old or female animals, respectively. However, SCFA receptor (GPR41 or GPR43) deficiency did not affect C2RD development. Thus, SCFAs, when systemically administered at levels higher than physiological levels, cause dysregulated T cell responses and tissue inflammation in the renal system. The results provide insights into the immunological and pathological effects of chronically elevated SCFAs.<\/jats:p>","DOI":"10.4049\/jimmunol.1502046","type":"journal-article","created":{"date-parts":[[2016,1,28]],"date-time":"2016-01-28T02:53:59Z","timestamp":1453949639000},"page":"2388-2400","source":"Crossref","is-referenced-by-count":152,"title":["Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell\u2013Mediated Ureteritis and Hydronephrosis"],"prefix":"10.1093","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0340-9181","authenticated-orcid":false,"given":"Jeongho","family":"Park","sequence":"first","affiliation":[{"name":"Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue University , West Lafayette, IN 47907"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8883-7953","authenticated-orcid":false,"given":"Craig J","family":"Goergen","sequence":"additional","affiliation":[{"name":"Weldon School of Biomedical Engineering, Purdue University , West Lafayette, IN 47907"},{"name":"Purdue Center for Cancer Research, Purdue University , West Lafayette, IN 47907"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2738-9189","authenticated-orcid":false,"given":"Harm","family":"HogenEsch","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue University , West Lafayette, IN 47907"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4618-9139","authenticated-orcid":false,"given":"Chang H","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue University , West Lafayette, IN 47907"},{"name":"Weldon School of Biomedical Engineering, Purdue University , West Lafayette, IN 47907"},{"name":"Purdue Center for Cancer Research, Purdue University , West Lafayette, IN 47907"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,3,1]]},"reference":[{"key":"2025030702135397100_r1","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1136\/gut.28.10.1221","article-title":"Short chain fatty acids in human large intestine, portal, hepatic and venous blood","volume":"28","author":"Cummings","year":"1987","journal-title":"Gut"},{"key":"2025030702135397100_r2","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.cmet.2011.02.018","article-title":"The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon","volume":"13","author":"Donohoe","year":"2011","journal-title":"Cell Metab."},{"key":"2025030702135397100_r3","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1073\/pnas.2637002100","article-title":"Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41","volume":"101","author":"Xiong","year":"2004","journal-title":"Proc. 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