IFN-γ Induces PD-L1 Expression in Primed Human Basophils

Abstract

Programmed death-ligand 1 (PD-L1) plays a key role in maintaining immune tolerance and also in immune evasion of cancers and pathogens. Though the identity of stimuli that induce PD-L1 in various human innate cells and their function are relatively well studied, data on the basophils remain scarce. In this study, we have identified one of the factors, such as IFN-γ, that induces PD-L1 expression in human basophils. Interestingly, we found that basophil priming by IL-3 is indispensable for IFN-γ-induced PD-L1 expression in human basophils. However, priming by other cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF) and thymic stromal lymphopoietin (TSLP) was dispensable. Analyses of a published microarray data set on IL-3-treated basophils indicated that IL-3 enhances IFNGR2, one of the chains of the IFNGR heterodimer complex, and CD274, thus providing a mechanistic insight into the role of IL-3 priming in IFN-γ-induced PD-L1 expression in human basophils.

Sequential engagement of adhesion molecules and cytokine receptors impacts both piecemeal and anaphylactic degranulation of human basophils

“…Our focus has been human basophil biology, and we focus on selected key factors involved in basophil migration such as crosslinking and cytokine exposure We have focused on two cytokines, IL-3 and IL-33, which have main impact in the circulation and at the tissue level, respectively. However, one ought to consider that a variety of other cytokines are operational in tuning basophil characteristics, for example, gamma Interferon [29].…”

Pathogenic accumulation of T follicular helper cells in lupus disease depends on PD-L1 and IL-4 expressing basophils

“…PD-L1 expression by basophils is known in humans and may be induced by IFNγ 37 . PD-L1 upregulation on human basophils has recently been described during SARS-CoV2 infections 38 although it is not directly induced by the virus 39 .…”

“…pDC or follicular DC and basophils may indeed compete to engage PD-1 on TFH cells to respectively inhibit or promote TFH cell expansion and TFH2 cell differentiation in EF responses in an autoimmune context. PD-L1 expression by basophils is known in humans and may be induced by IFNγ 37 . PD-L1 upregulation on human basophils has recently been described during SARS-CoV2 infections 38 although it is not directly induced by the virus 39 .…”

Incursions by severe acute respiratory syndrome coronavirus-2 on the host anti-viral immunity during mild, moderate, and severe coronavirus disease 2019 disease

“…Lastly, although not discussed due to lack of data, there are many unanswered questions about asymptomatic cases with SARS-CoV-2 infection, as these cases significantly contribute to viral spread globally. Therefore, in these individuals, there is a need to delineate the role of viral load and virus-shedding dynamics as opposed to symptomatic cases, which will facilitate the understanding of onward transmission, disease length, and severity, and the possible biomarkers [77] that could segregate asymptomatic from mild, moderate, and severe categories.…”