CD14++CD16+ Monocytes Are Enriched by Glucocorticoid Treatment and Are Functionally Attenuated in Driving Effector T Cell Responses.
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.
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Baoying
B
Liu
School of Clinical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom; National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London EC1V 2PD, United Kingdom; and.
Ashwin
A
Dhanda
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Sima
S
Hirani
School of Clinical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom; National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London EC1V 2PD, United Kingdom; and.
Emily L
EL
Williams
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
H Nida
HN
Sen
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Fernando
F
Martinez Estrada
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Diamond
D
Ling
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Ian
I
Thompson
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Megan
M
Casady
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Zhiyu
Z
Li
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Han
H
Si
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
William
W
Tucker
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Lai
L
Wei
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Shayma
S
Jawad
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Amol
A
Sura
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Jennifer
J
Dailey
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Susan
S
Hannes
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Ping
P
Chen
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
Jason L
JL
Chien
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Siamon
S
Gordon
School of Clinical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom; National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London EC1V 2PD, United Kingdom; and.
Richard W J
RW
Lee
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892; drbob@nei.nih.gov.
Robert B
RB
Nussenblatt
D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D058851:GPI-Linked Proteins / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D014605:Uveitis / Q000276:immunology
C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D005938:Glucocorticoids; C508609:IL10 protein, human; D020381:Interleukin-17; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D016753:Interleukin-10; D003907:Dexamethasone; D007371:Interferon-gamma