Human TCRγδ+ T cells represent a novel target for IL-27 activity.
IL-27 and TCRγδ(+)  T lymphocytes play critical roles in both innate and adaptive immune responses in health and disease, including infection and tumors. Although the activity of IL-27 is well characterized in different human immune cells, no information is available on the role of IL-27 in human TCRγδ(+)  T lymphocytes. Here, we provide the first evidence that TCRγδ(+)  T lymphocytes express both gp130 and WSX-1 chains of IL-27R, and that IL-27 may function in TCRγδ(+)  T cells by (i) inducing STAT1 and STAT3 phosphorylation, (ii) stimulating cytotoxicity against tumor cells through upregulation of cytotoxic granules production, (iii) reducing the release of Th2-related cytokines, such as IL-5 and IL-13, and inducing IFN-γ production, and (iv) upregulating the expression of CD62L. These results highlighted a novel immunoregulatory property of human IL-27 that may be relevant in the immune response against tumors. Our results may offer new perspectives for the development of future clinical trials using IL-27 and TCRγδ(+)  cells for cancer immunotherapy.
Laboratory of Oncology, G. Gaslini Institute, Genova, Italy.
Fabio
F
Morandi
Ignazia
I
Prigione
Irma
I
Airoldi
D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007378:Interleukins / Q000502:physiology*; D019041:L-Selectin / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000502:physiology; D018123:Receptors, Interleukin / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; C112441:IL27RA protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; D019041:L-Selectin