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Dendritic cell-expressed common gamma-chain recruits IL-15 for trans-presentation at the murine immunological synapse [version 2; referees: 2 approved]

Beilin, C; Choudhuri, K; Bouma, G; Malinova, D; Llodra, J; Stokes, DL; Shimaoka, M; ... Burns, SO; + view all (2018) Dendritic cell-expressed common gamma-chain recruits IL-15 for trans-presentation at the murine immunological synapse [version 2; referees: 2 approved]. Wellcome Open Research , 3 , Article 84. 10.12688/wellcomeopenres.14493.2. Green open access

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Abstract

BACKGROUND: Mutations of the common cytokine receptor gamma chain (γc) cause Severe Combined Immunodeficiency characterized by absent T and NK cell development. Although stem cell therapy restores these lineages, residual immune defects are observed that may result from selective persistence of γc-deficiency in myeloid lineages. However, little is known about the contribution of myeloid-expressed γc to protective immune responses.  Here we examine the importance of γc for myeloid dendritic cell (DC) function. METHODS: We utilize a combination of in vitro DC/T-cell co-culture assays and a novel lipid bilayer system mimicking the T cell surface to delineate the role of DC-expressed γc during DC/T-cell interaction. RESULTS: We observed that γc in DC was recruited to the contact interface following MHCII ligation, and promoted IL-15Rα colocalization with engaged MHCII. Unexpectedly, trans-presentation of IL-15 was required for optimal CD4+T cell activation by DC and depended on DC γc expression. Neither recruitment of IL-15Rα nor IL-15 trans-signaling at the DC immune synapse (IS), required γc signaling in DC, suggesting that γc facilitates IL-15 transpresentation through induced intermolecular cis associations or cytoskeletal reorganization following MHCII ligation. CONCLUSION: These findings show that DC-expressed γc is required for effective antigen-induced CD4+ T cell activation. We reveal a novel mechanism for recruitment of DC IL-15/IL-15Rα complexes to the IS, leading to CD4+ T cell costimulation through localized IL-15 transpresentation that is coordinated with antigen-recognition.

Type: Article
Title: Dendritic cell-expressed common gamma-chain recruits IL-15 for trans-presentation at the murine immunological synapse [version 2; referees: 2 approved]
Open access status: An open access version is available from UCL Discovery
DOI: 10.12688/wellcomeopenres.14493.2
Publisher version: https://doi.org/10.12688/wellcomeopenres.14493.2
Language: English
Additional information: © 2018 Beilin C et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: interleukins, immunological synapse, immunodeficiency, trans-presentation, dendritic cells, lymphocyte
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: http://discovery.ucl.ac.uk/id/eprint/10063442
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