CD14++CD16+ Monocytes Are Enriched by Glucocorticoid Treatment and Are Functionally Attenuated in Driving Effector T Cell Responses

Baoying Liu, Ashwin Dhanda, Sima Hirani, Emily L. Williams, H. Nida Sen, Estrada F Martinez, Diamond Ling, Ian Thompson, Megan Casady, Zhiyu Li, Han Si, William Tucker, Lai Wei, Shayma Jawad, Amol Sura, Jennifer Dailey, Susan Hannes, Ping Chen, Jason L. Chien, Siamon GordonRichard W.J. Lee, Robert B. Nussenblatt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

<jats:title>Abstract</jats:title> <jats:p>Human peripheral monocytes have been categorized into three subsets based on differential expression levels of CD14 and CD16. However, the factors that influence the distribution of monocyte subsets and the roles that each subset plays in autoimmunity are not well studied. In this study, we show that circulating monocytes from patients with autoimmune uveitis exhibit a skewed phenotype toward intermediate CD14++CD16+ cells, and that this is associated with glucocorticoid therapy. We further demonstrate that CD14++CD16+ monocytes from patients and healthy control donors share a similar cell-surface marker and gene expression profile. Comparison of the effects of intermediate CD14++CD16+ monocytes with classical CD14++CD16− and nonclassical CD14+CD16++ monocytes revealed that the intermediate CD14++CD16+ subset had an attenuated capacity to promote both naive CD4+ T cell proliferation and polarization into a Th1 phenotype, and memory CD4+ T cell proliferation and IL-17 expression. Furthermore, CD14++CD16+ cells inhibit CD4+ T cell proliferation induced by other monocyte subsets and enhance CD4+ T regulatory cell IL-10 expression. These data demonstrate the impact of glucocorticoids on monocyte phenotype in the context of autoimmune disease and the differential effects of monocyte subsets on effector T cell responses.</jats:p>
Original languageEnglish
Pages (from-to)5150-5160
Number of pages0
JournalThe Journal of Immunology
Volume194
Issue number11
DOIs
Publication statusPublished - 1 Jun 2015

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