CD5 expression promotes IL-10 production through activation of the MAPK/Erk pathway and upregulation of TRPC1 channels in B lymphocytes

作     者：Soizic Garaud Taher E Taher Marjolaine Debant Miguel Burgos Sarra Melayah Christian Berthou Kaushal Parikh Jacques-Olivier Pers Damien Luque-Paz Gilles Chiocchia Maikel Peppelenbosch David A Isenberg Pierre Youinou Olivier Mignen Yves Renaudineau Rizgar A Mageed 

作者机构：INSERM ERI29/EA2216réseau epigenetique and réseau canaux ioniques du Cancéropôle Grand OuestBrest University Medical SchoolBrest29609France Centre for Experimental Medicine and RheumatologyWilliam Harvey Research InstituteBarts and the London School of Medicine and DentistryQueen Mary University of LondonLondonEC1M 6BQUK Canalopathy and Calcium SignalingINSERM UMR1078Brest29238France Centre for Experimental and Molecular MedicineAcademic Medical CenterMeibergdreef 9Amsterdam1105 AZThe Netherlands Laboratory of Immunology and ImmunotherapyCHU MorvanBrest29609France Institut CochinINSERM U567Paris75014France Department of Gastroenterology and HepatologyErasmus MCGravendijkwal 230Rotterdam015 CERotterdamThe Netherlands Centre for RheumatologyUniversity College LondonLondonWC1E 6JFUK 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2018年第15卷第2期

页      面：158-170页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by a grant from Arthritis Research-UK to RAM and by grants from the “Canceropole Grand Ouest” the “Region Bretagne” and the “Ligue contre le cancer” to YR 

主　　题：B cells calcium CD5 MAPK/Erk TRPC1 

摘      要：CD5 is constitutively expressed on T cells and a subset of mature normal and leukemic B cells in patients with chronic lymphocytic leukemia(CLL).Important functional properties are associated with CD5 expression in B cells,including signal transducer and activator of transcription 3 activation,IL-10 production and the promotion of B-lymphocyte survival and ***,the pathway(s)by which CD5 influences the biology of B cells and its dependence on B-cell receptor(BCR)co-signaling remain *** this study,we show that CD5 expression activates a number of important signaling pathways,including Erk1/2,leading to IL-10 production through a novel pathway independent of BCR *** pathway is dependent on extracellular calcium(Ca2+)entry facilitated by upregulation of the transient receptor potential channel 1(TRPC1)*** also show that Erk1/2 activation in a subgroup of CLL patients is associated with TRPC1 *** this subgroup of CLL patients,small inhibitory RNA(siRNA)for CD5 reduces TRPC1 ***,siRNAs for CD5 or for TRPC1 inhibit IL-10 *** findings provide new insights into the role of CD5 in B-cell biology in health and disease and could pave the way for new treatment strategies for patients with B-CLL.