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journal article Dec 07, 2018

STAT6 inhibitory peptide reduces dendritic cell migration to the lymph nodes to control Th2 adaptive immunity in the mouse lung

Soojin Lee ORCID Jichuan Shan Haya Aldossary Véronique Gaudreault Mark Bazett Elizabeth D Fixman ORCID
European Journal of Immunology Vol. 49 No. 1 pp. 157-169 · Wiley
View at Publisher Save 10.1002/eji.201847534
Abstract
AbstractType 2 immunity in the lung is promoted through the release of innate cytokines, including TSLP, from lung structural cells. These cytokines drive Type 2 immunity in part through upregulation of OX40L on dendritic cells (DCs). DCs expressing OX40L are potent inducers of Th2 differentiation. We have shown previously that STAT6 inhibitory peptide (STAT6‐IP), a cell penetrating peptide designed to inhibit the STAT6 transcription factor, reduces the induction of Th2 adaptive immunity in murine models of respiratory syncytial virus infection. Here we show that intranasal administration of STAT6‐IP at the time of antigen priming with ovalbumin (OVA), in conjunction with the Nod2 agonist, MDP, reduced frequencies of CD11b+ lung DCs expressing OX40L. Consistent with these reductions, fewer activated DCs were localized to the lung draining lymph nodes in STAT6‐IP‐treated mice. Upon OVA challenge four weeks later, mice treated with STAT6‐IP at the time of OVA/MDP priming did not develop airway hyperresponsiveness (AHR) and had reduced influx of eosinophils into the airways, mucus production, and serum OVA‐specific IgE levels. Our findings provide evidence that the long‐lasting inhibitory effects of STAT6‐IP are due in part to inhibition of DC responses that drive maladaptive Th2 adaptive immunity and allergic airways disease.
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Showing 50 of 68 references

Metrics
19
Citations
68
References
Details
Published
Dec 07, 2018
Vol/Issue
49(1)
Pages
157-169
License
View
Authors
S
Soojin Lee

Meakins‐Christie Laboratories Research Institute of the McGill University Health Centre Montréal Québec Canada

J
Jichuan Shan

Meakins‐Christie Laboratories Research Institute of the McGill University Health Centre Montréal Québec Canada

H
Haya Aldossary

Meakins‐Christie Laboratories Research Institute of the McGill University Health Centre Montréal Québec Canada

V
Véronique Gaudreault

Meakins‐Christie Laboratories Research Institute of the McGill University Health Centre Montréal Québec Canada

M
Mark Bazett

Meakins‐Christie Laboratories Research Institute of the McGill University Health Centre Montréal Québec Canada

E
Elizabeth D Fixman

Meakins‐Christie Laboratories Research Institute of the McGill University Health Centre Montréal Québec Canada

Funding
Canadian Institutes of Health Research Award: MOP 106487
U.S. Department of Defense Award: W81XWH‐15‐1‐0697
Cite This Article
Soojin Lee, Jichuan Shan, Haya Aldossary, et al. (2018). STAT6 inhibitory peptide reduces dendritic cell migration to the lymph nodes to control Th2 adaptive immunity in the mouse lung. European Journal of Immunology, 49(1), 157-169. https://doi.org/10.1002/eji.201847534
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