Abstract
During type 1 immune responses, CD4 T helper 1 (Th1) cells and CD8 T cells are activated via IL-12 and contribute to the elimination of intracellular pathogens through interferon gamma (IFNγ) production. In this study, we identified Placenta-specific 8 (Plac8) as a gene that is uniquely expressed in Th1 CD4 T cells relative to other CD4 T cell subsets and hypothesized that Plac8 may represent a novel therapeutic target in Th1 CD4 T cells. First, we determined that Plac8 mRNA in CD4 T cells was induced following IL-12 stimulation via an indirect route that required new protein synthesis. Upon evaluating the functional relevance of Plac8 expression in Th1 CD4 T cells, we discovered that Plac8 was important for suppressing IFNγ mRNA and protein production by CD4 T cells 24 hours after IL-12 stimulation, however Plac8 did not contribute to pathogenic CD4 T cell function during two models of intestinal inflammation. We also noted relatively high basal expression of Plac8 in CD8 T cells which could be further induced following IL-12 stimulation in CD8 T cells. Furthermore, Plac8 expression was important for establishing an optimal CD8 T cell response against influenza A virus via a T cell-intrinsic manner. Altogether, these results implicate Plac8 as a potential regulator of Th1 CD4 and CD8 T cell responses during Th1 T cell-driven inflammation.
Highlights
We show that Placenta-specific 8 (Plac8) mRNA is differentially expressed by T helper 1 (Th1) CD4 T cells compared to Th2, Th17, and iTreg T helper subsets differentiated in vitro
We have determined that Plac8 is highly and uniquely expressed by Th1 CD4 T cells compared to Th2, Th17, and iTreg CD4 T cells
We found that Plac8 is indirectly induced following IL-12 stimulation in CD4 T cells and that IFNγ plays a modest role in its induction
Summary
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Type 1 cell-mediated immune responses consist of CD4 T helper 1 (Th1) cells and CD8 cytotoxic T cells that provide protection against intracellular pathogens primarily through secretion of interferon gamma (IFNγ) and tumor necrosis factor (TNF) following IL-12 stimulation [1, 2]. Dysregulation of type I immune responses can lead to autoimmune disorders such as rheumatoid arthritis, multiple sclerosis, or inflammatory bowel disease [3].
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