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

Cellular & Molecular Immunology volume 15, pages 158–170 (2018)Cite this article

Abstract

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.

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Acknowledgements

This study was supported by a grant from Arthritis Research-UK to RAM and by grants from the “Cancéropole Grand Ouest”, the “Région Bretagne” and the “Ligue contre le cancer” to YR. We thank Catherine Riou and Professor Valérie Ugo (Brest) for the clinical material and Ms Simone Forest and Geneviève Michel for helping with typing the manuscript.

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Author notes

  1. Soizic Garaud and Taher E Taher: These authors contributed equally to this study.

  2. Yves Renaudineau and Rizgar A Mageed: These authors contributed equally as senior authors to this study.

Authors and Affiliations

  1. INSERM ERI29/EA2216, réseau epigenetique and réseau canaux ioniques du Cancéropôle Grand Ouest, Brest University Medical School, Brest, 29609, France

    Soizic Garaud, Marjolaine Debant, Sarra Melayah, Christian Berthou, Jacques-Olivier Pers, Damien Luque-Paz, Pierre Youinou & Yves Renaudineau

  2. Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK

    Taher E Taher & Rizgar A Mageed

  3. Canalopathy and Calcium Signaling, INSERM UMR1078, Brest, 29238, France

    Miguel Burgos & Olivier Mignen

  4. Centre for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands

    Kaushal Parikh

  5. Laboratory of Immunology and Immunotherapy, CHU Morvan, Brest, 29609, France

    Damien Luque-Paz & Yves Renaudineau

  6. Institut Cochin, INSERM U567, Paris, 75014, France

    Gilles Chiocchia

  7. Department of Gastroenterology and Hepatology, Erasmus MC, Gravendijkwal 230, Rotterdam, 015 CE, Rotterdam, The Netherlands

    Maikel Peppelenbosch

  8. Centre for Rheumatology, University College London, London, WC1E 6JF, UK

    David A Isenberg

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  1. Soizic Garaud
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Correspondence to Rizgar A Mageed.

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Garaud, S., Taher, T., Debant, M. et al. CD5 expression promotes IL-10 production through activation of the MAPK/Erk pathway and upregulation of TRPC1 channels in B lymphocytes. Cell Mol Immunol 15, 158–170 (2018). https://doi.org/10.1038/cmi.2016.42

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