Multi-Tissue Characterization of GILZ Expression in Dendritic Cell Subsets at Steady State and in Inflammatory Contexts.

Molène Docq,Françoise Mercier-Nomé,Françoise Bachelerie,Agnieszka Jaracz-Ros,Géraldine Schlecht-Louf,Mathias Vétillard,Carmen Gallego

doi:10.3390/cells10113153

Abstract

Dendritic cells (DCs) are key players in the control of tolerance and immunity. Glucocorticoids (GCs) are known to regulate DC function by promoting their tolerogenic differentiation through the induction of inhibitory ligands, cytokines, and enzymes. The GC-induced effects in DCs were shown to critically depend on increased expression of the Glucocorticoid-Induced Leucine Zipper protein (GILZ). GILZ expression levels were further shown to control antigen-presenting cell function, as well as T-cell priming capacity of DCs. However, the pattern of GILZ expression in DC subsets across tissues remains poorly described, as well as the modulation of its expression levels in different pathological settings. To fill in this knowledge gap, we conducted an exhaustive analysis of GILZ relative expression levels in DC subsets from various tissues using multiparametric flow cytometry. This study was performed at steady state, in the context of acute as well as chronic skin inflammation, and in a model of cancer. Our results show the heterogeneity of GILZ expression among DC subsets as well as the complexity of its modulation, that varies in a cell subset- and context-specific manner. Considering the contribution of GILZ in the control of DC functions and its potential as an immune checkpoint in cancer settings, these results are of high relevance for optimal GILZ targeting in therapeutic strategies.

Highlights

IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Our work provides the most exhaustive map of Glucocorticoid-Induced Leucine Zipper protein (GILZ)
Our results established that GILZ expression levels by Dendritic cells (DCs) vary depending on the Our results established that GILZ expression levels by DCs vary depending on the subset and tissue of interest at steady state

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Appropriate induction of tolerance or immunity is critical for limiting immunemediated pathologies, like autoimmune diseases and allergies, while favoring protective anti-infectious and -cancer responses. Dendritic cells (DCs) are key players in this equilibrium [1]. They form a heterogeneous family of potent professional antigen presenting cells (APCs) that encompasses ontogenetically- and functionally-defined subsets, currently classified as plasmacytoid (p)DCs, type 1 and 2 conventional DCs (cDC1 and cDC2), and monocyte-derived DCs in both human and mouse [1–3]. Dermal cDCs are further divided in CD103+ and CD103− cDC1 cells, CD11b+ cDC2 and CD11b− CD103−

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