Placenta-specific 8 limits IFNγ production by CD4 T cells in vitro and promotes establishment of influenza-specific CD8 T cells in vivo

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.

A zebrafish model for COVID-19 recapitulates olfactory and cardiovascular pathophysiologies caused by SARS-CoV-2

“…Further, we detected a noticeable decrease in the proportion of cells belonging to the Lymphocyte2 cluster, a cluster that expressed markers of Treg cells ( foxp3b ) 3 h post intranasal delivery of recombinant SARS-CoV-2 S RBD but this change was not noticeable at day 3 (Figure 4C). At 3 d, we observed a third lymphocyte cluster, not detected at 3 h, highly expressing the TCR subunit zap70 as well as plac8 onzin related protein ( ponzr1 ), a molecule that has immunoregulatory roles during Th1 type immune responses in mammals (Figure S2) (Slade et al, 2020). These results indicate important cellular responses in neuronal and immune cell subsets of the zebrafish olfactory organ in response to SARS-CoV-2 S RBD.…”

Multifaced roles of PLAC8 in cancer

“…PLAC8 exists in a variety of immune cells and the level of PLAC8 varies in different immune cells. PLAC8 is higher expressed by Th1 CD4 T-cells compared to Th2, Th17 and iTreg CD4 T-cells [22]. In addition, PLAC8 is relatively highly expressed in airway T helper 2 (Th2) cells which play a pathogenic role in allergies [98].…”

“…For example, PLAC8 suppresses the production of the pro-inflammatory cytokines, IL-1b and IL-18, via enhancement of autophagy in adult-onset Still's disease [74]. PLAC8 is important for suppressing IFNγ production by IL-12 stimulation in CD4 T-cell [22]. And CD4 T-cell expression of PLAC8 correlates with potent termination of Chlamydia replication and relative independence from IFNγ pretreatment of epithelial monolayers [100,101].…”

“…PLAC8 acts as a transcription factor involved in the expression of different genes. In CD4 T cells, PLAC8 suppresses IL-12-induced IFNγ production at the transcriptional level [22]. PLAC8 binds to the C/EBPβ promoter to induce its transcription [26].…”

“…To date, PLAC8 has been determined to be involved in organ development and tumorigenesis [18][19][20][21]. In addition, PLAC8 is a molecular marker to predict prognosis and distinguish between different cell subpopulations [17,22]. PLAC8 also plays different roles in a cell-or tissue-type specific manner.…”