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Cited by 13Sinusitis and nasal conditionsCystic Fibrosis Research AdvancesT-cell and B-cell Immunology

Selective expansion of human regulatory T cells in nasal polyps, and not adjacent tissue microenvironments, in individual patients exposed to steroids

Edward, Justin A, Sanyal, Mrinmoy, Le, Wei, Soudry, Ethan, Ramakrishnan, Vijay R, Bravo, Dawn T, Nguyen, Alan L, Zarabanda, David +4 more·2017·Clinical Immunology
DOI 10.1016/j.clim.2017.02.002
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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 reg) cells. T reg 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 reg 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 reg 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 reg 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 reg cells from peripheral sites into NP tissues, which may be critical to the anti-inflammatory effect of GCs. Mechanistically T reg expansion appears to be conferred, in part, by chemokine receptor/ligand interactions induced following corticosteroid therapy.

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Crossref · 10.1016/j.clim.2017.02.002

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  • CS promote M2 macrophage polarization, induce T regulatory cell recruitment and expansion, Th1 to Th2 phenotype skewing, and apoptosis in lymphocytes, thereby blunting a proliferative burst of CD8-positive T cells needed in cancer response to PD-1/PD-L1 blockade.

    “CS, the most widely used immunosuppressants, promote M2 macrophage polarization, 36 induce T regulatory cells recruitment and expansions, 37 Th1 to Th2 phenotype skewing, 38 and apoptosis in lymphocytes, 39 thereby blunting a proliferative burst of CD8-positive T cells needed in cancer response to PD-1/PD-L-1 blockade.40”

    From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [37]

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Authors
Edward, J. A., Sanyal, M., Le, W., Soudry, E., Ramakrishnan, V. R., Bravo, D. T., Nguyen, A. L., Zarabanda, D., Kingdom, T. T., Hwang, P. H., Garrison Fathman, C., & Nayak, J. V.
Affiliations
  • Stanford Medicine (US)
  • Tel Aviv University (IL)
  • University of Colorado Anschutz (US)
Corresponding author
Nayak, Jayakar V
ORCID
Venue
Clinical Immunology
Publisher
Elsevier BV
Published
2017-06
Volume
179
Pages
66-76
ISSN
1521-6616 (ISSN-L)
DOI
10.1016/j.clim.2017.02.002
OpenAlex
W2594045629
Cited by
13
References
56
Citations by year
2024: 3 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1
FWCI
1.71
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Stanford University
  • University of Colorado
  • American Academy of Otolaryngology-Head and Neck Surgery/Triologic Society
  • P30 Core Facilities (DC010363)
Topics
  • Health Sciences › Medicine › Otorhinolaryngology › Sinusitis and nasal conditions
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
regulatory T cells, nasal polyps, chronic rhinosinusitis, glucocorticoid therapy, chemokines, carbon tetrachloride, CCR4 antagonist, Treg cell migration, Ki-67, tissue microenvironment, anti-inflammatory mechanism
MeSH terms
Biopsy, Chronic Disease, Glucocorticoids, Humans, Nasal Polyps, Prednisone, Rhinitis, Sinusitis, Chemokines, Gene Expression Profiling, T-Lymphocytes, Regulatory, Forkhead Transcription Factors

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