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Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s.

Citation
von Moltke, J., et al. “Leukotrienes Provide An Nfat-Dependent Signal That Synergizes With Il-33 To Activate Ilc2S.”. The Journal Of Experimental Medicine, pp. 27-37.
Author Jakob von Moltke, Claire E O'Leary, Nora A Barrett, Yoshihide Kanaoka, Frank Austen, Richard M Locksley
Abstract

Group 2 innate lymphoid cells (ILC2s) and type 2 helper T cells (Th2 cells) are the primary source of interleukin 5 (IL-5) and IL-13 during type 2 (allergic) inflammation in the lung. In Th2 cells, T cell receptor (TCR) signaling activates the transcription factors nuclear factor of activated T cells (NFAT), nuclear factor κB (NF-κB), and activator protein 1 (AP-1) to induce type 2 cytokines. ILC2s lack a TCR and respond instead to locally produced cytokines such as IL-33. Although IL-33 induces AP-1 and NF-κB, NFAT signaling has not been described in ILC2s. In this study, we report a nonredundant NFAT-dependent role for lipid-derived leukotrienes (LTs) in the activation of lung ILC2s. Using cytokine reporter and LT-deficient mice, we find that complete disruption of LT signaling markedly diminishes ILC2 activation and downstream responses during type 2 inflammation. Type 2 responses are equivalently attenuated in IL-33- and LT-deficient mice, and optimal ILC2 activation reflects potent synergy between these pathways. These findings expand our understanding of ILC2 regulation and may have important implications for the treatment of airways disease.

Year of Publication
2017
Journal
The Journal of experimental medicine
Volume
214
Issue
1
Number of Pages
27-37
Date Published
12/2017
ISSN Number
1540-9538
DOI
10.1084/jem.20161274
Alternate Journal
J. Exp. Med.
PMID
28011865
PMCID
PMC5206504
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