RORγt-Raftlin1 complex regulates the pathogenicity of Th17 cells and colonic inflammation.

Autor: Singh AK; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA., Kumar R; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA., Yin J; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA., Brooks Ii JF; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, 75390, USA., Kathania M; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA., Mukherjee S; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA., Kumar J; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA., Conlon KP; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA., Basrur V; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA., Chen Z; Department of Biophysics, UT Southwestern Medical Center, Dallas, TX, 75390, USA., Han X; University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA., Hooper LV; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.; The Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX, 75390, USA., Burstein E; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA., Venuprasad K; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA. venuprasad.poojary@UTSouthwestern.edu.; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, 75390, USA. venuprasad.poojary@UTSouthwestern.edu.; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA. venuprasad.poojary@UTSouthwestern.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Aug 17; Vol. 14 (1), pp. 4972. Date of Electronic Publication: 2023 Aug 17.
DOI: 10.1038/s41467-023-40622-1
Abstrakt: Th17 cells that produce Interleukin IL-17 are pathogenic in many human diseases, including inflammatory bowel disease, but are, paradoxically, essential for maintaining the integrity of the intestinal barrier in a non-inflammatory state. However, the intracellular mechanisms that regulate distinct transcriptional profiles and functional diversity of Th17 cells remain unclear. Here we show Raftlin1, a lipid raft protein, specifically upregulates and forms a complex with RORγt in pathogenic Th17 cells. Disruption of the RORγt-Raftlin1 complex results in the reduction of pathogenic Th17 cells in response to Citrobacter rodentium; however, there is no effect on nonpathogenic Th17 cells in response to commensal segmented filamentous bacteria. Mechanistically, we show that Raftlin1 recruits distinct phospholipids to RORγt and promotes the pathogenicity of Th17 cells. Thus, we have identified a mechanism that drives the pathogenic function of Th17 cells, which could provide a platform for advanced therapeutic strategies to dampen Th17-mediated inflammatory diseases.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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