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

Abstract

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 which each subset plays in autoimmunity are not well studied. Here we show that circulating monocytes from patients with autoimmune uveitis exhibit a skewed phenotype towards 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 non-classical CD14+CD16++ monocytes revealed that the intermediate CD14++CD16+ subset had an attenuated capacity to promote both naïve 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.

T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells

“…Whether, this latter subset displays suppressive function is controversial. For some authors, these cells do produce the antiproliferative cytokine IL-10 or induce T reg s, [44][45][46] whereas for others, they highly express HLA-DR and release the proinflammatory cytokine tumor necrosis factor a. 47 Proliferation Index [27][28][29]39 M-MDSCs were recently defined, in tumor-bearing mice, as the most immunosuppressive subset.…”

Single-cell profiling of Ebola virus infectionin vivoreveals viral and host transcriptional dynamics

“…TNF α signaling has been extensively implicated as a driver of systemic loss of vascular resistance and shock during EVD. Glucocorticoids have been less well studied in EVD, but decrease MHC-II ex vivo (Hawrylowicz et al, 1994) and in vivo during sepsis (Tulzo et al, 2004) and reduce CD14 expression (Nockher and Scherberich, 1997) while increasing the abundance of DP monocytes (Liu et al, 2015) . Indeed, the connection between EVD and sepsis may be direct: studies have found bacterial invasion during EVD in NHPs (Reisler et al, 2018) and in humans (Carroll et al, 2017) , with immune signatures that resemble sepsis (Eisfeld et al, 2017) .…”

Characteristics of dendritic cells from patients with rheumatoid arthritis and different type of drug therapy

“…Данные о влиянии глюкокортикоидов на субпопуляци-онный состав моноцитов у больных РА отсут-ствуют. Тем не менее показано, что при ауто-иммунном увеите терапия глюкокортикоидами приводит к селективному накоплению промежу-точных (CD14++CD16+) моноцитов, которые ин-гибируют пролиферацию Т-клеток и индуцируют генерацию Т-рег [38]. Относительно биологиче-ских препаратов L. Chara c соавт.…”