FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313330084> ?p ?o ?g. }

• W4313330084 abstract "Abstract Introduction Gut microbiota plays a critical role in the regulation of immune homeostasis. Accordingly, several autoimmune disorders have been associated with dysbiosis in the gut microbiota. Notably, the dysbiosis associated with central nervous system (CNS) autoimmunity involves a substantial reduction of bacteria belonging to Clostridia clusters IV and XIVa, which constitute major producers of short-chain fatty acids (SCFA). Here we addressed the role of the surface receptor-mediated effects of SCFA on mucosal T-cells in the development of CNS autoimmunity. Methods To induce CNS autoimmunity we used the mouse model of experimental autoimmune encephalomyelitis (EAE) induced by immunization with the myelin oligodendrocyte glycoprotein (MOG)-derived peptide (MOG 35 − 55 peptide). To address the effects of GPR43 stimulation on colonic TCRαβ + T-cells upon CNS autoimmunity, mucosal lymphocytes were isolated and stimulated with a selective GPR43 agonist ex vivo and then transferred into congenic mice undergoing EAE. Several subsets of lymphocytes infiltrating the CNS or those present in the gut epithelium and gut lamina propria were analysed by flow cytometry. In vitro migration assays were conducted with mucosal T-cells using transwells. Results Our results show a sharp and selective reduction of intestinal propionate at the peak of EAE development, accompanied by increased IFN-γ and decreased IL-22 in the colonic mucosa. Further analyses indicated that GPR43 was the primary SCFA receptor expressed on T-cells, which was downregulated on colonic TCRαβ + T-cells upon CNS autoimmunity. The pharmacologic stimulation of GPR43 increased the anti-inflammatory function and reduced the pro-inflammatory features in several TCRαβ + T-cell subsets in the colonic mucosa upon EAE development. Furthermore, GPR43 stimulation induced the arrest of CNS-autoreactive T-cells in the colonic lamina propria, thus avoiding their infiltration into the CNS and dampening the disease development. Mechanistic analyses revealed that GPR43-stimulation on mucosal TCRαβ + T-cells inhibits their CXCR3-mediated migration towards CXCL11, which is released from the CNS upon neuroinflammation. Conclusions These findings provide a novel mechanism involved in the gut-brain axis by which bacterial-derived products secreted in the gut mucosa might control the CNS tropism of autoreactive T-cells. Moreover, this study shows GPR43 expressed on T-cells as a promising therapeutic target for CNS autoimmunity." @default.
• W4313330084 created "2023-01-06" @default.
• W4313330084 creator A5009961267 @default.
• W4313330084 creator A5022019480 @default.
• W4313330084 creator A5026573989 @default.
• W4313330084 creator A5029107903 @default.
• W4313330084 creator A5055357094 @default.
• W4313330084 creator A5060309568 @default.
• W4313330084 creator A5066180141 @default.
• W4313330084 date "2022-12-29" @default.
• W4313330084 modified "2023-10-16" @default.
• W4313330084 title "GPR43 stimulation on TCRαβ+ intraepithelial colonic lymphocytes inhibits the recruitment of encephalitogenic T-cells into the central nervous system and attenuates the development of autoimmunity" @default.
• W4313330084 cites W1941562583 @default.
• W4313330084 cites W1963769931 @default.
• W4313330084 cites W1972691065 @default.
• W4313330084 cites W1981266729 @default.
• W4313330084 cites W1989957107 @default.
• W4313330084 cites W1993078298 @default.
• W4313330084 cites W2002368408 @default.
• W4313330084 cites W2003342633 @default.
• W4313330084 cites W2016693701 @default.
• W4313330084 cites W2035421462 @default.
• W4313330084 cites W2037907937 @default.
• W4313330084 cites W2048469790 @default.
• W4313330084 cites W2056279562 @default.
• W4313330084 cites W2060185417 @default.
• W4313330084 cites W2078780781 @default.
• W4313330084 cites W2080295265 @default.
• W4313330084 cites W2086427126 @default.
• W4313330084 cites W2096618637 @default.
• W4313330084 cites W2099857099 @default.
• W4313330084 cites W2100051740 @default.
• W4313330084 cites W2101662803 @default.
• W4313330084 cites W2107369528 @default.
• W4313330084 cites W2112999168 @default.
• W4313330084 cites W2119522619 @default.
• W4313330084 cites W2121968767 @default.
• W4313330084 cites W2132411790 @default.
• W4313330084 cites W2154490180 @default.
• W4313330084 cites W2162704444 @default.
• W4313330084 cites W2166839330 @default.
• W4313330084 cites W2179438025 @default.
• W4313330084 cites W2200372542 @default.
• W4313330084 cites W2337334490 @default.
• W4313330084 cites W2342375154 @default.
• W4313330084 cites W2395861697 @default.
• W4313330084 cites W2401404581 @default.
• W4313330084 cites W2409656339 @default.
• W4313330084 cites W2539337648 @default.
• W4313330084 cites W2574682203 @default.
• W4313330084 cites W2589854016 @default.
• W4313330084 cites W2748155559 @default.
• W4313330084 cites W2752435500 @default.
• W4313330084 cites W2756015955 @default.
• W4313330084 cites W2756391458 @default.
• W4313330084 cites W2783654020 @default.
• W4313330084 cites W2799443654 @default.
• W4313330084 cites W2800002566 @default.
• W4313330084 cites W2911938169 @default.
• W4313330084 cites W2942689716 @default.
• W4313330084 cites W2947545169 @default.
• W4313330084 cites W2950081364 @default.
• W4313330084 cites W2960154753 @default.
• W4313330084 cites W2966388959 @default.
• W4313330084 cites W2996473783 @default.
• W4313330084 cites W2998403567 @default.
• W4313330084 cites W3002007664 @default.
• W4313330084 cites W3034476589 @default.
• W4313330084 cites W3067885102 @default.
• W4313330084 cites W3108392891 @default.
• W4313330084 cites W3158872698 @default.
• W4313330084 cites W3162691867 @default.
• W4313330084 cites W3169398005 @default.
• W4313330084 cites W4224240736 @default.
• W4313330084 cites W4225564674 @default.
• W4313330084 cites W4313379132 @default.
• W4313330084 doi "https://doi.org/10.21203/rs.3.rs-2406632/v1" @default.
• W4313330084 hasPublicationYear "2022" @default.
• W4313330084 type Work @default.
• W4313330084 citedByCount "0" @default.
• W4313330084 crossrefType "posted-content" @default.
• W4313330084 hasAuthorship W4313330084A5009961267 @default.
• W4313330084 hasAuthorship W4313330084A5022019480 @default.
• W4313330084 hasAuthorship W4313330084A5026573989 @default.
• W4313330084 hasAuthorship W4313330084A5029107903 @default.
• W4313330084 hasAuthorship W4313330084A5055357094 @default.
• W4313330084 hasAuthorship W4313330084A5060309568 @default.
• W4313330084 hasAuthorship W4313330084A5066180141 @default.
• W4313330084 hasBestOaLocation W43133300841 @default.
• W4313330084 hasConcept C203014093 @default.
• W4313330084 hasConcept C2777165150 @default.
• W4313330084 hasConcept C2777899865 @default.
• W4313330084 hasConcept C2778486448 @default.
• W4313330084 hasConcept C2779357208 @default.
• W4313330084 hasConcept C2780130043 @default.
• W4313330084 hasConcept C2780640218 @default.
• W4313330084 hasConcept C539455810 @default.
• W4313330084 hasConcept C86803240 @default.
• W4313330084 hasConcept C8891405 @default.
• W4313330084 hasConceptScore W4313330084C203014093 @default.

• next