ER Stress Regulates Immunosuppressive Function of Myeloid Derived Suppressor Cells in Leprosy that Can Be Overcome in the Presence of IFN-γ

Kindra M Kelly-Scumpia; Aaron Choi; Roksana Shirazi; Hannah Bersabe; Esther Park; Philip O Scumpia; Maria T Ochoa; Jing Yu; Feiyang Ma; Matteo Pellegrini; Robert L Modlin

doi:10.1016/j.isci.2020.101050

ER Stress Regulates Immunosuppressive Function of Myeloid Derived Suppressor Cells in Leprosy that Can Be Overcome in the Presence of IFN-γ

iScience. 2020 May 22;23(5):101050. doi: 10.1016/j.isci.2020.101050. Epub 2020 Apr 12.

Authors

Affiliations

¹ Division of Dermatology, David Geffen School of Medicine, Los Angeles, CA 90095, USA. Electronic address: kkellyscumpia@mednet.ucla.edu.
² Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.
³ Division of Dermatology, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
⁴ Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
⁵ Division of Dermatology, David Geffen School of Medicine, Los Angeles, CA 90095, USA; Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.

Abstract

Myeloid derived suppressor cells (MDSCs) are a population of immature myeloid cells that suppress adaptive immune function, yet the factors that regulate their suppressive function in patients with infection remain unclear. We studied MDSCs in patients with leprosy, a disease caused by Mycobacterium leprae, where clinical manifestations present on a spectrum that correlate with immunity to the pathogen. We found that HLA-DR^-CD33⁺CD15⁺ MDSCs were increased in blood from patients with disseminated/progressive lepromatous leprosy and possessed T cell-suppressive activity as compared with self-limiting tuberculoid leprosy. Mechanistically, we found ER stress played a critical role in regulating the T cell suppressive activity in these MDSCs. Furthermore, ER stress augmented IL-10 production, contributing to MDSC activity, whereas IFN-γ allowed T cells to overcome MDSC suppressive activity. These studies highlight a regulatory mechanism that links ER stress to IL-10 in mediating MDSC suppressive function in human infectious disease.

Keywords: Biological Sciences; Cell Biology; Functional Aspects of Cell Biology; Immune Response; Immunology.

Abstract

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