Activation of VIP signaling enhances immunosuppressive effect of MDSCs on CMV-induced adaptive immunity.

Parvin Forghani,Christopher T Petersen,Edmund K Waller

doi:10.18632/oncotarget.20704

Parvin Forghani, Christopher T Petersen + Show 1 more

Open Access

https://doi.org/10.18632/oncotarget.20704

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Journal: Oncotarget	Publication Date: Sep 7, 2017
Citations: 8	License type: cc-by

Affiliation: Emory University

Abstract

Vasoactive intestinal peptide (VIP) is recognized as a potent anti-inflammatory factor which affects both the innate and adaptive arms of the immune system. These effects include, but are not limited to, inhibition of T cell proliferation and disruption of immune homeostasis. Myeloid-derived suppressor cells (MDSC) are an immune regulatory cell type that has been described in settings of cancer and infectious disease._Here we demonstrate a reduced circulating monocytic MDSCs in the VIP -/- vs. wild type MCMV. VIP-/- MDSCs secretes less NO upon stimulation with LPS and interferon that relatively lose the ability to suppress T cells activation in vitro compared to wild type MDSCs._Considering the importance of VIP in immunomodulation, the possible effect of VIP in the suppressive function of MDSC populations following CMV infection remains unknown. We describe the possible role of VIP in the regulation of anti-CMV activity of T cells through the activation of MDSCs.

Highlights

Myeloid-derived suppressor cells (MDSC) are identified as monocytic and granulocyticCD11b+ GR-1+ populations of immature myeloid cells that are expanded in malignant states, bacterial infections, and fungal infections [1,2,3]
There were no significant differences in the absolute number and frequency of immature myeloid cells (IMC) or total white blood cell count (WBC) in the blood when comparing Vasoactive intestinal peptide (VIP)/− mice to wild type at baseline (Figure 1A)
Analyzing the phenotypes of sub populations of MDSC showed a population of Ly6Clo/med cells in VIP−/− mice that was not observed in the wild type counterpart

Summary

Introduction

MDSC are identified as monocytic and granulocyticCD11b+ GR-1+ populations of immature myeloid cells that are expanded in malignant states, bacterial infections, and fungal infections [1,2,3] They play a vital role in disease modulation of cancer and chronic inflammatory illnesses through suppression of CD4+ and/or CD8+ T cell function [4,5,6]. VIP inhibits the production of inflammatory cytokines and chemokines from macrophages, microglia and dendritic cells through the VIP receptors VPAC1 and VPAC2 [10] These receptors are widely distributed throughout the body, including cells of the immune system and VPAC1 up regulated by inflammation [9]. MDSCs contribute to tumor-associated antigen-specific T cell dysfunction and tolerance [6, 14]

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