IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39
Ivan D. Mascanfroni,Ada Yeste,Silvio M. Vieira,Evan J Burns,Bonny Patel,Ido Sloma,Yan Wu,Lior Mayo,Rotem Ben-Hamo,Sol Efroni,Vijay K. Kuchroo,Simon C. Robson,Francisco J. Quintana +12 more
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TLDR
Interleukin 27 (IL-27) signaling in mouse DCs limited the generation of effector cells of the TH1 and TH17 subsets of helper T cells and the development of experimental autoimmune encephalomyelitis (EAE).Abstract:
Dendritic cells (DCs) control the balance between effector T cells and regulatory T cells in vivo. Hence, the study of DCs might identify mechanisms of disease pathogenesis and guide new therapeutic approaches for disorders mediated by the immune system. We found that interleukin 27 (IL-27) signaling in mouse DCs limited the generation of effector cells of the TH1 and TH17 subsets of helper T cells and the development of experimental autoimmune encephalomyelitis (EAE). The effects of IL-27 were mediated at least in part through induction of the immunoregulatory molecule CD39 in DCs. IL-27-induced CD39 decreased the extracellular concentration of ATP and downregulated nucleotide-dependent activation of the NLRP3 inflammasome. Finally, therapeutic vaccination with IL-27-conditioned DCs suppressed established relapsing-remitting EAE. Thus, IL-27 signaling in DCs limited pathogenic T cell responses and the development of autoimmunity.read more
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Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor
Veit Rothhammer,Ivan D. Mascanfroni,Lukas Bunse,Maisa C. Takenaka,Jessica E. Kenison,Lior Mayo,Chun-Cheih Chao,Bonny Patel,Raymond Yan,Manon Blain,Jorge I. Alvarez,Hania Kebir,Niroshana Anandasabapathy,Guillermo Izquierdo,Steffen Jung,Nikolaus D. Obholzer,Nikolaus D. Obholzer,Nathalie Pochet,Nathalie Pochet,Clary B. Clish,Marco Prinz,Alexandre Prat,Jack P. Antel,Francisco J. Quintana +23 more
TL;DR: Findings suggest that IFN-Is produced in the CNS function in combination with metabolites derived from dietary tryptophan by the gut flora to activate AHR signaling in astrocytes and suppress CNS inflammation.
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The P2X7 Receptor in Infection and Inflammation
TL;DR: The central role played by the P2X7 receptor in promoting inflammation and driving innate and adaptive immunity is discussed, with an in‐depth knowledge of its structure and of the associated signal transduction mechanisms needed for an effective therapeutic development.
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The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease.
TL;DR: The role of AHR in autoimmune and neoplastic diseases of the central nervous system, with a special focus on the gut immune system, the gut–brain axis and the therapeutic potential of targeting A HR in neurological disorders are discussed.
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The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets.
TL;DR: Insight into potential clinical application of adenosinergic and other purinergic‐targeting therapies and forecast how these might develop in combination with other anti‐cancer modalities are provided.
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Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases
Mübeccel Akdis,Alar Aab,Can Altunbulakli,Kursat A Azkur,Rita Costa,Reto Crameri,Su Duan,Thomas Eiwegger,Andrzej Eljaszewicz,Ruth Ferstl,Remo Frei,Mattia Garbani,Anna Głobińska,Lena Hess,Carly Huitema,Terufumi Kubo,Zsolt István Komlósi,Patricia Konieczna,Nóra Kovács,Umut Can Kucuksezer,Norbert Meyer,Hideaki Morita,Judith Olzhausen,Liam O'Mahony,Marija Pezer,Moira Prati,Ana Rebane,Claudio Rhyner,Arturo Rinaldi,Milena Sokolowska,Barbara Stanic,Kazunari Sugita,Angela Treis,Willem van de Veen,Kerstin Wanke,Marcin Wawrzyniak,Paulina Wawrzyniak,Oliver F. Wirz,Josefina Zakzuk,Cezmi A. Akdis +39 more
TL;DR: Recent developments on IL-1 to IL-38, TNF-α, TGF-β, and interferons are reviewed and their cellular sources, targets, receptors, signaling pathways, and roles in immune regulation in patients with allergy and asthma and other inflammatory diseases are discussed.
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