Distinct inflammatory Th17 subsets emerge in autoimmunity and infection
Th17 cells play a critical role in both tissue homeostasis and inflammation during clearance of infections as well as autoimmune and inflammatory disorders. Despite numerous efforts to distinguish the homeostatic and inflammatory roles of Th17 cells, the mechanism underlying the divergent functions...
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| Veröffentlicht in: | The Journal of experimental medicine 2023-10, Vol.220 (10) |
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| container_title | The Journal of experimental medicine |
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| creator | Bouch, Ronald J Zhang, Jing Miller, Brandi C Robbins, Caroline J Mosher, Timothy H Li, Wencheng Krupenko, Sergey A Nagpal, Ravinder Zhao, Jun Bloomfeld, Richard S Lu, Yong Nikiforov, Mikhail A Song, Qianqian He, Zhiheng |
| description | Th17 cells play a critical role in both tissue homeostasis and inflammation during clearance of infections as well as autoimmune and inflammatory disorders. Despite numerous efforts to distinguish the homeostatic and inflammatory roles of Th17 cells, the mechanism underlying the divergent functions of inflammatory Th17 cells remains poorly understood. In this study, we demonstrate that the inflammatory Th17 cells involved in autoimmune colitis and those activated during colitogenic infection are distinguishable populations characterized by their differential responses to the pharmacological molecule, clofazimine (CLF). Unlike existing Th17 inhibitors, CLF selectively inhibits proautoimmune Th17 cells while preserving the functional state of infection-elicited Th17 cells partially by reducing the enzyme ALDH1L2. Overall, our study identifies two distinct subsets within the inflammatory Th17 compartment with distinct regulatory mechanisms. Furthermore, we highlight the feasibility to develop disease-promoting Th17 selective inhibitor for treating autoimmune diseases. |
| doi_str_mv | 10.1084/jem.20221911 |
| format | Article |
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Despite numerous efforts to distinguish the homeostatic and inflammatory roles of Th17 cells, the mechanism underlying the divergent functions of inflammatory Th17 cells remains poorly understood. In this study, we demonstrate that the inflammatory Th17 cells involved in autoimmune colitis and those activated during colitogenic infection are distinguishable populations characterized by their differential responses to the pharmacological molecule, clofazimine (CLF). Unlike existing Th17 inhibitors, CLF selectively inhibits proautoimmune Th17 cells while preserving the functional state of infection-elicited Th17 cells partially by reducing the enzyme ALDH1L2. Overall, our study identifies two distinct subsets within the inflammatory Th17 compartment with distinct regulatory mechanisms. Furthermore, we highlight the feasibility to develop disease-promoting Th17 selective inhibitor for treating autoimmune diseases.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20221911</identifier><identifier>PMID: 37367944</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Autoimmune Diseases ; Autoimmunity ; Brief Definitive Report ; Colitis ; Humans ; Inflammation ; Metabolism ; Mucosal Immunology ; Th17 Cells</subject><ispartof>The Journal of experimental medicine, 2023-10, Vol.220 (10)</ispartof><rights>2023 Bouch et al.</rights><rights>2023 Bouch et al. 2023 Bouch et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-a75ce7c8509442588b8c8b5106dad3707d3db452c87acd7754e19f71f458ad953</citedby><cites>FETCH-LOGICAL-c385t-a75ce7c8509442588b8c8b5106dad3707d3db452c87acd7754e19f71f458ad953</cites><orcidid>0000-0002-6926-2776 ; 0000-0001-8862-2960 ; 0000-0002-4250-1749 ; 0000-0002-6039-4377 ; 0000-0002-4455-5302 ; 0000-0002-6986-999X ; 0009-0006-8377-9567 ; 0000-0002-4176-8249 ; 0000-0002-0088-178X ; 0009-0000-3177-8622 ; 0000-0003-0077-0040 ; 0009-0000-7581-7355 ; 0000-0001-9976-0920 ; 0000-0001-7868-0518</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37367944$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bouch, Ronald J</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Miller, Brandi C</creatorcontrib><creatorcontrib>Robbins, Caroline J</creatorcontrib><creatorcontrib>Mosher, Timothy H</creatorcontrib><creatorcontrib>Li, Wencheng</creatorcontrib><creatorcontrib>Krupenko, Sergey A</creatorcontrib><creatorcontrib>Nagpal, Ravinder</creatorcontrib><creatorcontrib>Zhao, Jun</creatorcontrib><creatorcontrib>Bloomfeld, Richard S</creatorcontrib><creatorcontrib>Lu, Yong</creatorcontrib><creatorcontrib>Nikiforov, Mikhail A</creatorcontrib><creatorcontrib>Song, Qianqian</creatorcontrib><creatorcontrib>He, Zhiheng</creatorcontrib><title>Distinct inflammatory Th17 subsets emerge in autoimmunity and infection</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Th17 cells play a critical role in both tissue homeostasis and inflammation during clearance of infections as well as autoimmune and inflammatory disorders. 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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Autoimmune Diseases Autoimmunity Brief Definitive Report Colitis Humans Inflammation Metabolism Mucosal Immunology Th17 Cells |
| title | Distinct inflammatory Th17 subsets emerge in autoimmunity and infection |
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