IL-37 inhibits IL-4/IL-13-induced CCL11 production and lung eosinophilia in murine allergic asthma.

Abstract

BACKGROUND:

IL-37 is emerging as an anti-inflammatory cytokine, particularly in innate inflammation. However, the role of IL-37 in Th2-mediated allergic lung inflammation remains uncertain. We sought to determine the role and the underlying mechanisms of IL-37 in the development of house dust mites (HDM)-induced murine asthma model.

METHODS:

We examined the effect of IL-37 administration during the sensitization or challenge phase on Th2-mediated allergic asthma induced by inhaled HDM. Cellular source of CCL11 and distribution of IL-37 receptors, IL-18Rα and IL-1R8, were determined in HDM-exposed lungs. Finally, we examined the effect of IL-37 on CCL11 production and STAT6 activation in different primary lung structural cell types upon IL-4/IL-13 stimulation.

RESULTS:

IL-37 had no effect on HDM sensitization, but when administrated during the challenge phase, significantly attenuated pulmonary eosinophilia, CCL11 production, and airway hyper-reactivity (AHR). Interestingly, IL-37 treatment had no significant effects on lung infiltrating T cells and Th2 cytokine production. Intranasal co-administration of CCL11 reversed the inhibiting effect of IL-37 on HDM-induced pulmonary eosinophilia and AHR. Furthermore, we demonstrated that CCL11 was primarily expressed by fibroblasts and airway smooth muscle cells (AMSC), while IL-37 receptors by tracheobronchial epithelial cells (TEC). In vitro study showed that IL-37 inhibited IL-4/IL-13-induced STAT6 activation and CCL11 production by fibroblasts and AMSC, which was dependent on its direct action on TEC. Moreover, cell contact was required for the inhibitory effect of IL-37-treated TEC.

CONCLUSIONS:

IL-37 attenuates HDM-induced asthma, possibly by inhibiting IL-4/IL-13-induced CCL11 production by fibroblasts and AMSC via its direct act on TEC.

• Authors: J Lv, Y Xiong, W Li, X Cui, X Cheng, Q Leng, R He
• Journal: Allergy (Allergy) Vol. 73 Issue 8 Pg. 1642-1652 (Aug 2018) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 29319845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Chemical References

• Ccl11 protein, mouse
• Chemokine CCL11
• IL37 protein, human
• Interleukin-1
• Interleukin-13
• STAT6 Transcription Factor
• Stat6 protein, mouse
• Interleukin-4

Topics

• Analysis of Variance
• Animals
• Asthma (drug therapy, etiology, immunology)
• Chemokine CCL11 (antagonists & inhibitors)
• Disease Models, Animal
• Interleukin-1 (administration & dosage, pharmacology, therapeutic use)
• Interleukin-13 (metabolism)
• Interleukin-4 (metabolism)
• Mice
• Mice, Inbred BALB C
• Pulmonary Eosinophilia (drug therapy, etiology, immunology)
• Pyroglyphidae
• STAT6 Transcription Factor (metabolism)
• Th2 Cells (immunology)