IL-17

Interleukin (IL)-17 (IL-17) is a pro-inflammatory cytokine that is mainly produced by activated CD4+ T cells. Besides, IL-17 is also secreted by other multiple immune cell types, including invariant natural killer T cells, CD8+ T cells, lymphoid tissue inducer (LTi)-like cells, and gamma delta T (γδ T) cells. IL-17 secreted by γδ T cells has been shown to exert diverse effects including promoting the growth and metastasis of tumor cells, eradicating infections of pathogenic microorganisms, and promoting bone regeneration.

Pro-tumor Role of IL-17-producing γδ T cells

Some studies showed IL-17-producing γδ T cells may promote tumorigenesis. In mouse models of spontaneous breast cancer metastasis, IL-17-producing γδ T cells in cooperation with neutrophils were shown to promote breast cancer metastasis. IL-17-producing γδ T cells can promote the tumor-associated neutrophils (TAN) expansion, accumulation, phenotype in a granulocyte colony-stimulating factor (G-CSF)-dependent manner in breast tumors. These TANs display immunosuppressive functions by suppressing effector cytotoxic T lymphocyte (CTL) function, thereby promoting the metastasis of breast cancer cells. Besides, IL-17-producing γδ T cells have been shown to recruit macrophage subsets expressing high levels of IL-17 receptor which are associated with the proliferation of ovarian cancer cells and colorectal cancer cells. Interestingly, IL-17-producing γδ T cell infiltration are positively associated with clinical stage and other clinicopathological characterizations of colorectal cancer, indicating the potential of IL-17-producing γδ T cells in the prognosis of colorectal cancer.

Fig.1 IL-17A promotes tumor growth in hepatocellular carcinoma murine models. (Ma, 2014)

Bone Regeneration

IL-17-producing γδ T cells have been shown to promote bone formation and facilitate bone fracture healing. IL-17A is highly induced immediately after bone injury and promotes bone regeneration by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells. IL-17-producing γδ T cells provide a promising therapeutic approach for bone fracture healing.

Fig.2 IL-17A enhances bone formation by injury-associated mesenchymal cells. (Ono, 2016)

Infectious Diseases

IL-17-producing γδ T cells, as innate-like lymphocytes, play an essential role in host defense against pathogenic microorganisms such as Listeria monocytogenes, Toxoplasma Gondii, and Clostridium difficile. In mice with C. difficile infections, the IL-17 production by intestinal γδ T cells was efficiently increased, which could be resistant to C. difficile infections.

Creative Biolabs has focused on the function and characteristics of γδ T cells for several years. We can leverage our expertise and comprehensive research technologies to support all-around γδ T cell research involving the development of γδ T cell therapy, analysis of γδ T cell receptor, γδ T cell development, and γδ T cell engineering. If you are interested in these, please contact us for more details.

References

1. Ma, S.; et al. IL-17A produced by γδ T cells promotes tumor growth in hepatocellular carcinoma. Cancer Res. 74(7):1969-1982.
2. Ono, T.; et al. IL-17-producing γδ T cells enhance bone regeneration. Nat Commun. 2016, 7: 10928.