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IL-4R is expressed on alpha and beta cells of human pancreata.

S. Rajendran,Madeleine Graef,Tiffany Chu,M. V. von Herrath

Published 2020 in Clinical Immunology

ABSTRACT

Type 1 diabetes (T1D) is widely regarded as a Th1-mediated disease, where beta cell killing is facilitated by IFN-γ driven activation of CD8+ T cells and macrophages [1,2]. T1D is often accompanied by reduction in Th2 responses, for instance, stimulated PBMC or T cells from patients with recent onset T1D exhibit reduced capability of secreting IL-4 [3]. IL-4, being a major driver of Th2 polarization, was extensively studied in the context of preventing T1D, due to its antagonizing effects on Th1 responses. Several studies in the NOD mice in the 1990s reported that i) expression of IL-4 in the beta cells of NOD mice model prevents insulitis and incidence of T1D [4], and ii) treatment of NOD with recombinant IL-4 prevents diabetes and reverses T cell proliferative unresponsiveness before the onset of diabetes [5,6]. IL-4-mediated protection from T1D is reported to be driven by activation of non-pathogenic T cell clones [7] and induction of regulatory function of Th2 cells [8]. In addition, exposure of isolated human islet cultures to IL-4 has been shown to protect islets from pro-inflammatory cytokine induced cell death, mainly though activation of the STAT6 pathway [9,10]. It is not clearly understood whether the protective effect of IL-4 in preventing T1D is solely due to localized immunosuppression in T cells or in part due to IL-4R signaling in beta cells. There are also contradicting evidences regarding the expression of IL-4R in human pancreas. IL-4R expression has been reported to be expressed in human islets at both protein [6] and mRNA [11] levels. Levels of IL-4R mRNA in human islets were further enhanced upon infection with Coxsackie virus B (CVB) or treatment with pro-inflammatory cytokine cocktail [12]. Contrarily, data from human protein atlas suggests low or no expression of IL-4R in islets of human pancreas [13]. This area has been relatively unexplored in nearly a decade, warranting subsequent studies. Hence, we reinvestigated the expression of IL-4R in human pancreas and traced its cellular source using multiplex florescence imaging.

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