Contribution of the SYK Tyrosine kinase expression to human iNKT self-reactivity.

Autor: Perroteau J; Université de Nantes, CNRS, Inserm, CRCINA, Nantes, France., Navet B; Université de Nantes, CNRS, Inserm, CRCINA, Nantes, France., Devilder MC; Université de Nantes, CHU Nantes, CNRS, Inserm, CRCINA, Nantes, France., Hesnard L; Université de Nantes, CNRS, Inserm, CRCINA, Nantes, France., Scotet E; Université de Nantes, CNRS, Inserm, CRCINA, Nantes, France., Gapin L; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA., Saulquin X; Université de Nantes, CNRS, Inserm, CRCINA, Nantes, France., Gautreau-Rolland L; Université de Nantes, CNRS, Inserm, CRCINA, Nantes, France.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2020 Oct; Vol. 50 (10), pp. 1454-1467. Date of Electronic Publication: 2020 Jun 08.
DOI: 10.1002/eji.201948416
Abstrakt: Invariant Natural Killer T (iNKT) cells are particular T lymphocytes at the frontier between innate and adaptative immunities. They participate in the elimination of pathogens or tumor cells, but also in the development of allergic reactions and autoimmune diseases. From their first descriptions, the phenomenon of self-reactivity has been described. Indeed, they are able to recognize exogenous and endogenous lipids. However, the mechanisms underlying the self-reactivity are still largely unknown, particularly in humans. Using a CD1d tetramer-based sensitive immunomagnetic approach, we generated self-reactive iNKT cell lines from blood circulating iNKT cells of healthy donors. Analysis of their functional characteristics in vitro showed that these cells recognized endogenous lipids presented by CD1d molecules through their TCR that do not correspond to α-glycosylceramides. TCR sequencing and transcriptomic analysis of T cell clones revealed that a particular TCR signature and an expression of the SYK protein kinase were two mechanisms supporting human iNKT self-reactivity. The SYK expression, strong in the most self-reactive iNKT clones and variable in ex vivo isolated iNKT cells, seems to decrease the activation threshold of iNKT cells and increase their overall antigenic sensitivity. This study indicates that a modulation of the TCR intracellular signal contributes to iNKT self-reactivity.
(© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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