Structural basis of species-selective antagonist binding to the succinate receptor.

Related Articles Structural basis of species-selective antagonist binding to the succinate receptor. Nature. 2019 Oct;574(7779):581-585 Authors: Haffke M, Fehlmann D, Rummel G, Boivineau J, Duckely M, Gommermann N, Cotesta S, Sirockin F, Freuler F, Littlewood-Evans A, Kaupmann K, Jaakola VP Abstract The tricarboxylic acid cycle intermediate succinate is involved in metabolic processes and plays a crucial role in the homeostasis of mitochondrial reactive oxygen species1. The receptor responsible for succinate signalling, SUCNR1 (also known as GPR91), is a member of the G-protein-coupled-receptor family2 and links succinate signalling to renin-induced hypertension,…

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Analysis of the B cell receptor repertoire in six immune-mediated diseases.

Related Articles Analysis of the B cell receptor repertoire in six immune-mediated diseases. Nature. 2019 Sep 25;: Authors: Bashford-Rogers RJM, Bergamaschi L, McKinney EF, Pombal DC, Mescia F, Lee JC, Thomas DC, Flint SM, Kellam P, Jayne DRW, Lyons PA, Smith KGC Abstract B cells are important in the pathogenesis of many, and perhaps all, immune-mediated diseases. Each B cell expresses a single B cell receptor (BCR)1, and the diverse range of BCRs expressed by the total B cell population of an individual is termed the ‘BCR repertoire’. Our understanding…

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Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis.

Related Articles Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis. Nature. 2019 Sep 11;: Authors: Newton K, Wickliffe KE, Dugger DL, Maltzman A, Roose-Girma M, Dohse M, Kőműves L, Webster JD, Dixit VM Abstract The aspartate-specific cysteine protease caspase-8 suppresses necroptotic cell death mediated by RIPK3 and MLKL. Indeed, mice that lack caspase-8 die in a RIPK3- and MLKL-dependent manner during embryogenesis1-3. In humans, caspase-8 deficiency is associated with immunodeficiency4 or very early onset inflammatory bowel disease5. The substrates that are cleaved by caspase-8 to prevent necroptosis…

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Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Related Articles Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019 May;569(7758):655-662 Authors: Lloyd-Price J, Arze C, Ananthakrishnan AN, Schirmer M, Avila-Pacheco J, Poon TW, Andrews E, Ajami NJ, Bonham KS, Brislawn CJ, Casero D, Courtney H, Gonzalez A, Graeber TG, Hall AB, Lake K, Landers CJ, Mallick H, Plichta DR, Prasad M, Rahnavard G, Sauk J, Shungin D, Vázquez-Baeza Y, White RA, IBDMDB Investigators, Braun J, Denson LA, Jansson JK, Knight R, Kugathasan S, McGovern DPB, Petrosino JF, Stappenbeck TS, Winter HS, Clish CB, Franzosa EA,…

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Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2.

Related Articles Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2. Nature. 2019 Apr 03;: Authors: Zhou L, Chu C, Teng F, Bessman NJ, Goc J, Santosa EK, Putzel GG, Kabata H, Kelsen JR, Baldassano RN, Shah MA, Sockolow RE, Vivier E, Eberl G, Smith KA, Sonnenberg GF Abstract Interleukin (IL)-2 is a pleiotropic cytokine that is necessary to prevent chronic inflammation in the gastrointestinal tract1-4. The protective effects of IL-2 involve the generation, maintenance and function of regulatory T (Treg) cells4-8, and the use of low…

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Colonic epithelial cell diversity in health and inflammatory bowel disease.

Related Articles Colonic epithelial cell diversity in health and inflammatory bowel disease. Nature. 2019 Feb 27;: Authors: Parikh K, Antanaviciute A, Fawkner-Corbett D, Jagielowicz M, Aulicino A, Lagerholm C, Davis S, Kinchen J, Chen HH, Alham NK, Ashley N, Johnson E, Hublitz P, Bao L, Lukomska J, Andev RS, Björklund E, Kessler BM, Fischer R, Goldin R, Koohy H, Simmons A Abstract The colonic epithelium facilitates host-microorganism interactions to control mucosal immunity, coordinate nutrient recycling and form a mucus barrier. Breakdown of the epithelial barrier underpins inflammatory bowel disease (IBD).…

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c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont.

c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature. 2018 Feb 07;: Authors: Xu M, Pokrovskii M, Ding Y, Yi R, Au C, Harrison OJ, Galan C, Belkaid Y, Bonneau R, Littman DR Abstract Both microbial and host genetic factors contribute to the pathogenesis of autoimmune diseases. There is accumulating evidence that microbial species that potentiate chronic inflammation, as in inflammatory bowel disease, often also colonize healthy individuals. These microorganisms, including the Helicobacter species, can induce pathogenic T cells and are collectively referred to as pathobionts. However,…

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Structure of the complement C5a receptor bound to the extra-helical antagonist NDT9513727.

Structure of the complement C5a receptor bound to the extra-helical antagonist NDT9513727. Nature. 2018 Jan 03;553(7686):111-114 Authors: Robertson N, Rappas M, Doré AS, Brown J, Bottegoni G, Koglin M, Cansfield J, Jazayeri A, Cooke RM, Marshall FH Abstract The complement system is a crucial component of the host response to infection and tissue damage. Activation of the complement cascade generates anaphylatoxins including C5a and C3a. C5a exerts a pro-inflammatory effect via the G-protein-coupled receptor C5a anaphylatoxin chemotactic receptor 1 (C5aR1, also known as CD88) that is expressed on cells of…

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Fine-mapping inflammatory bowel disease loci to single-variant resolution.

Fine-mapping inflammatory bowel disease loci to single-variant resolution. Nature. 2017 Jun 28;: Authors: Huang H, Fang M, Jostins L, Umićević Mirkov M, Boucher G, Anderson CA, Andersen V, Cleynen I, Cortes A, Crins F, D’Amato M, Deffontaine V, Dmitrieva J, Docampo E, Elansary M, Farh KK, Franke A, Gori AS, Goyette P, Halfvarson J, Haritunians T, Knight J, Lawrance IC, Lees CW, Louis E, Mariman R, Meuwissen T, Mni M, Momozawa Y, Parkes M, Spain SL, Théâtre E, Trynka G, Satsangi J, van Sommeren S, Vermeire S, Xavier RJ, International…

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