For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

Golgi Phosphoprotein 2 Is a Novel Regulator of IL-12 Production and Macrophage Polarization.

TitleGolgi Phosphoprotein 2 Is a Novel Regulator of IL-12 Production and Macrophage Polarization.
Publication TypeJournal Article
Year of Publication2018
AuthorsZhang W, Kim H, Lv J, Zhao N, Ma X
JournalJ Immunol
Volume200
Issue4
Pagination1480-1488
Date Published2018 02 15
ISSN1550-6606
KeywordsAnimals, Dendritic Cells, Gene Expression Regulation, Golgi Matrix Proteins, Interleukin-12, Macrophage Activation, Mice, Mice, Knockout
Abstract

Golgi phosphoprotein 2 (GOLPH2), a widely expressed Golgi type II transmembrane protein, has been implicated in several important physiological and pathological processes, including virus infections, cancer cell proliferation, and metastasis. However, its biological functions and mechanisms, particularly in the immune system, remain highly obscure. In this study, we report the biochemical identification of GOLPH2 from B cell lymphoma culture supernatant and show that the secreted protein could inhibit IL-12 production by dendritic cells (DCs) and IL-12-induced IFN-γ production by activated T cells. Further molecular analysis revealed that GOLPH2's IL-12-inhibiting activity was mediated through a proximal promoter element involving a previously identified transcriptional repressor named GC-binding protein that is induced during phagocytosis of apoptotic cells by macrophages. We subsequently generated global knockout mice, which exhibited little developmental abnormality but were more susceptible to LPS-induced endotoxic shock than were wild-type mice with elevated serum IL-12 levels. Furthermore, we found that GOLPH2 played a regulatory role in macrophage polarization toward the M2 type. A comprehensive analysis of gene expression profiles of activated wild-type and GOLPH2-deficient DCs by RNA sequencing uncovered mechanistic insights into the way GOLPH2 potentially modulates DC function during inflammatory insults. Our functional study of GOLPH2 helps advance the scientific understanding of the biological and pathogenic roles of this novel and intriguing molecule with great potential as a diagnostic and prognostic marker as well as a therapeutic target in many acute and chronic inflammatory disorders.

DOI10.4049/jimmunol.1700897
Alternate JournalJ Immunol
PubMed ID29298830

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587