| 1 | CD5 expression promotes IL-10 production through activation of the MAPK/Erk pathway and upregulation of TRPC1 channels in B lymphocytes显示文摘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 transformation.However,the pathway(s)by which CD5 influences the biology of B cells and its dependence on B-cell receptor(BCR)co-signaling remain unknown.In 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 engagement.This pathway is dependent on extracellular calcium(Ca2+)entry facilitated by upregulation of the transient receptor potential channel 1(TRPC1)protein.We also show that Erk1/2 activation in a subgroup of CLL patients is associated with TRPC1 overexpression.In this subgroup of CLL patients,small inhibitory RNA(siRNA)for CD5 reduces TRPC1 expression.Furthermore,siRNAs for CD5 or for TRPC1 inhibit IL-10 production.These 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. | 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 | 2018 | Cellular & Molecular Immunology2018，15，2： | 2 |
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