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Resolvin E1 regulates interleukin 23, interferon-γ and lipoxin A4 to promote the resolution of allergic airway inflammation

Abstract

Interleukin 23 (IL-23) is integral to the pathogenesis of chronic inflammation. The resolution of acute inflammation is an active process mediated by specific signals and mediators such as resolvin E1 (RvE1). Here we provide evidence that RvE1, in nanogram quantities, promoted the resolution of inflammatory airway responses in part by directly suppressing the production of IL-23 and IL-6 in the lung. Also contributing to the pro-resolution effects of RvE1 treatment were higher concentrations of interferon-γ in the lungs of RvE1-treated mice. Our findings indicate a pivotal function for IL-23 and IL-6, which promote the survival and differentiation of IL-17-producing T helper cells, in maintaining inflammation and also identify an RvE1-initiated resolution program for allergic airway responses.

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Figure 1: RvE1 dampens the development of allergic airway inflammation.
Figure 2: RvE1 promotes the resolution of airway inflammation.
Figure 3: RvE1 improves lung inflammation, airway mucus and airway hyper-reactivity.
Figure 4: RvE1 selectively regulates cytokine and lipid mediators.
Figure 5: RvE1 regulates the production of IL-17A and IFN-γ by T cells.
Figure 6: RvE1 and LXA4 use distinct mechanisms to promote the resolution of airway inflammation.

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Acknowledgements

We thank G.L. Zhu, B. Ith and K. Gotlinger for technical assistance. Supported by the US National Institutes of Health (AI068084 to B.D.L. and P50-DE016191 to B.D.L. and C.N.S.).

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O.H. did experiments and analyzed data, was involved in experimental design and wrote the manuscript; M.C. provided reagents, analyzed data and was involved in experimental design; R.Y. provided reagents; C.N.S. provided reagents, analyzed data, was involved in experimental design and helped write the manuscript; and B.D.L conceived the project, did and designed experiments, analyzed data and helped write the manuscript.

Corresponding author

Correspondence to Bruce D Levy.

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Competing interests

B.D.L. and C.N.S. are inventors on patents assigned to Brigham and Women's Hospital on the resolvins and their analogs that are licensed for clinical development and are the subject of consulting agreements.

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Haworth, O., Cernadas, M., Yang, R. et al. Resolvin E1 regulates interleukin 23, interferon-γ and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat Immunol 9, 873–879 (2008). https://doi.org/10.1038/ni.1627

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