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Selective expansion of human regulatory T cells in nasal polyps, and not adjacent tissue microenvironments, in individual patients exposed to steroids.
- Source :
-
Clinical immunology (Orlando, Fla.) [Clin Immunol] 2017 Jun; Vol. 179, pp. 66-76. Date of Electronic Publication: 2017 Mar 06. - Publication Year :
- 2017
-
Abstract
- Severe forms of chronic rhinosinusitis (CRS), a common upper airway inflammatory disorder, are associated with nasal polyps (NPs). NP disease is ameliorated by glucocorticoid (GC) treatment, whose cellular effects are poorly understood. We therefore assessed the influence of GC therapy on NPs in CRS patients, focusing on regulatory T (T <subscript>reg</subscript> ) cells. T <subscript>reg</subscript> cell populations were analyzed by flow cytometry in NPs and control tissues from GC-treated CRS patients and controls. After GC exposure, selective expansion of T <subscript>reg</subscript> cells was seen within NPs, and not blood or adjacent ethmoid tissues. To confirm direct GC effects, NPs from the same patients were biopsied prior to, and following, 1week of oral GC exposure. Direct expansion of Tregs into the same NP bed was detected in 4/4 CRS patients following GC exposure. T <subscript>reg</subscript> cell spikes into NPs were secondary to cellular recruitment given limited Ki67 expression within these regulatory cells. Chemokine gene expression profiling identified several chemokines, notably CCL4, induced within NPs upon GC treatment. Neutralization of chemokine receptor/ligand interactions using CCR4 small molecule antagonists reduced T <subscript>reg</subscript> migration towards GC-treated NPs in an ex vivo migration assay. Our findings suggest that the common use of GCs in the treatment of NP disease leads to recruitment of T <subscript>reg</subscript> cells from peripheral sites into NP tissues, which may be critical to the anti-inflammatory effect of GCs. Mechanistically T <subscript>reg</subscript> expansion appears to be conferred, in part, by chemokine receptor/ligand interactions induced following corticosteroid therapy.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Biopsy
Chemokines genetics
Chronic Disease
Forkhead Transcription Factors immunology
Gene Expression Profiling
Glucocorticoids therapeutic use
Humans
Nasal Polyps drug therapy
Nasal Polyps genetics
Nasal Polyps pathology
Prednisone therapeutic use
Rhinitis drug therapy
Rhinitis genetics
Rhinitis pathology
Sinusitis drug therapy
Sinusitis genetics
Sinusitis pathology
T-Lymphocytes, Regulatory immunology
Glucocorticoids pharmacology
Nasal Polyps immunology
Prednisone pharmacology
Rhinitis immunology
Sinusitis immunology
T-Lymphocytes, Regulatory drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1521-7035
- Volume :
- 179
- Database :
- MEDLINE
- Journal :
- Clinical immunology (Orlando, Fla.)
- Publication Type :
- Academic Journal
- Accession number :
- 28279811
- Full Text :
- https://doi.org/10.1016/j.clim.2017.02.002