Th9 Cells: A Novel CD4 T-cell Subset in the Immune War against Cancer
CANCER RESEARCH
Authors: Vegran, Frederique; Apetoh, Lionel; Ghiringhelli, Francois
Abstract
CD4 T cells are key components of the immune system that shape the anticancer immune response in animal models and in humans. The biology of CD4 T cells is complex because naive T cells can differentiate into various subpopulations with various functions. Recently, a new population called Th9 cells was described. These cells are characterized by their ability to produce IL9 and IL21. They were first described in the context of parasite infections and allergic processes. However, some reports described their presence in the tumor bed in mice and humans. Their high secretion of IL9 and IL21 in the tumor bed contributes to their anticancer functions. Indeed, these cytokines trigger the activation of dendritic cells, mast cells, natural killer cells, and CD8 T cells to mount an antitumor immune response, thus explaining the remarkable ability of Th9 cells to control tumor growth. This review summarizes the latest advances in the Th9 field in cancer and focuses on their potential role as new tool for cell therapy. (C) 2014 AACR.
Critics role of IL-21 and T follicular helper cells in hypertension and vascular dysfunction
JCI INSIGHT
Authors: Dale, Bethany L.; Pandey, Arvind K.; Chen, Yuhan; Smart, Charles D.; Laroumanie, Fanny; Ao, Mingfang; Xiao, Liang; Dikalova, Anna E.; Dikalov, Sergey, I; Elijovich, Fernando; Foss, Jason D.; Barbaro, Natalia R.; Van Beusecum, Justin P.; Deger, Serpil M.; Alsouqi, Aseel; Itani, Hana A.; Norlander, Allison E.; Alexander, Matthew R.; Zhao, Shilin; Ikizler, T. Alp; Algood, Holly M. Scott; Madhur, Meena S.
Abstract
T and B cells have been implicated in hypertension, but the mechanisms by which they produce a coordinated response is unknown. T follicular helper (Tfh) cells that produce IL-21 promote germinal center (GC) B cell responses, leading to lg production. Here we investigate the role of IL-21 and Tfh cells in hypertension. In response to angiotensin II-induced (Ang II-induced) hypertension, T cell IL-21 production was increased, and Il21(-/-) mice developed blunted hypertension, attenuated vascular end-organ damage, and decreased IL-17A and IFN-gamma production. Tfh-like cells and GC B cells accumulated in the aorta, and plasma IgG1 was increased in hypertensive WT but not or Il21(-/-) mice. Furthermore, Tfh cell-deficient mice developed blunted hypertension and vascular hypertrophy in response to Ang II infusion. Importantly, IL-21 neutralization reduced BP and reversed endothelial dysfunction and vascular inflammation. Moreover, recombinant IL-21 impaired endothelium-dependent relaxation ex vivo and decreased NO production from cultured endothelial cells. Finally, we show in humans that peripheral blood T cell production of IL-21 correlated with systolic BP and IL-17A production. These data suggest that IL-21 may be a novel therapeutic target for the treatment of hypertension and its micro- and macrovascular complications.