Immunology

Abstract

Interleukin 10 is a cytokine with the ability to reduce or terminate inflammation. Chronic viral infection, such as infection of chronic hepatitis B, hepatitis C and HIV, has increased levels of interleukin 10 in peripheral blood. Serum IL-10 levels are also high in certain cancers. Blocking IL-10 signalling at the time of immunisation clears chronic viral infection and prevents tumour growth in animal models. We review recent advances in this area, with the emphasis on potential use of this novel strategy to treat chronic viral infection and cancer in human.

Via Krishan Maggon

Highlights

 

•Spontaneous T cell responses against tumors require the host STING pathway in vivo•Tumor-derived DNA can induce type I interferon production via STING•Tumor DNA can be identified in host APCs in the tumor microenvironment in vivo

 

Summary

Spontaneous T cell responses against tumors occur frequently and have prognostic value in patients. The mechanism of innate immune sensing of immunogenic tumors leading to adaptive T cell responses remains undefined, although type I interferons (IFNs) are implicated in this process. We found that spontaneous CD8+T cell priming against tumors was defective in mice lacking stimulator of interferon genes complex (STING), but not other innate signaling pathways, suggesting involvement of a cytosolic DNA sensing pathway. In vitro, IFN-β production and dendritic cell activation were triggered by tumor-cell-derived DNA, via cyclic-GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3). In the tumor microenvironment in vivo, tumor cell DNA was detected within host antigen-presenting cells, which correlated with STING pathway activation and IFN-β production. Our results demonstrate that a major mechanism for innate immune sensing of cancer occurs via the host STING pathway, with major implications for cancer immunotherapy.

Via Krishan Maggon

Abstract

The interleukin-20 (IL-20) subfamily of cytokines comprises IL-19, IL-20, IL-22, IL-24 and IL-26. These cytokines are all members of the larger IL-10 family, but have been grouped together to form the IL-20 subfamily based on their usage of common receptor subunits and similarities in their target-cell profiles and biological functions. Members of the IL-20 subfamily facilitate the communication between leukocytes and epithelial cells, thereby enhancing innate defence mechanisms and tissue repair processes at epithelial surfaces. In this Review, we describe the cellular sources and targets of the IL-20 subfamily cytokines, and we detail how their expression is regulated. Much of our understanding of the unique biology of this group of cytokines is still based on IL-22, which is the most studied member of the IL-20 subfamily. Nevertheless, we attempt a broader discussion of the emerging functions of IL-20 subfamily cytokines in host defence, inflammatory diseases, cancer and metabolism.

Via Krishan Maggon