Nitric Oxide Synthase 2 Improves Proliferation and Glycolysis of Peripheral γδ T Cells.
γδ T cells play critical roles in host defense against infections and cancer. Although advances have been made in identifying γδ TCR ligands, it remains essential to understand molecular mechanisms responsible for in vivo expansion of γδ T cells in periphery. Recent findings identified the expression of the inducible NO synthase (NOS2) in lymphoid cells and highlighted novel immunoregulatory functions of NOS2 in αβ T cell differentiation and B cell survival. In this context, we wondered whether NOS2 exerts an impact on γδ T cell properties. Here, we show that γδ T cells express NOS2 not only in vitro after TCR triggering, but also directly ex vivo. Nos2 deficient mice have fewer γδ T cells in peripheral lymph nodes (pLNs) than their wild-type counterparts, and these cells exhibit a reduced ability to produce IL-2. Using chemical NOS inhibitors and Nos2 deficient γδ T cells, we further evidence that the inactivation of endogenous NOS2 significantly reduced γδ T cell proliferation and glycolysis metabolism that can be restored in presence of exogenous IL-2. Collectively, we demonstrate the crucial role of endogenous NOS2 in promoting optimal IL-2 production, proliferation and glycolysis of γδ T cells that may contribute to their regulation at steady state.
INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Laetitia
L
Douguet
Institut de Recherche sur le cancer et le vieillissement, CNRS UMR7284, INSERM U1081, Université de Nice, Nice, France.|Département de génétique médicale, Hôpital l'Archet, CHU de Nice, Nice, France.
Julien
J
Cherfils-Vicini
INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Lloyd
L
Bod
INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Renée
R
Lengagne
Institut de Recherche sur le cancer et le vieillissement, CNRS UMR7284, INSERM U1081, Université de Nice, Nice, France.|Département de génétique médicale, Hôpital l'Archet, CHU de Nice, Nice, France.
Eric
E
Gilson
INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Armelle
A
Prévost-Blondel
D000818:Animals; D049109:Cell Proliferation / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D006019:Glycolysis / Q000235:genetics* / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse