IL-37 Targets TSLP-Primed Basophils to Alleviate Atopic Dermatitis.

Abstract

Atopic dermatitis (AD) represents a severe global burden on physical, physiological and mental health. Innate immune cell basophils are essential for provoking allergic inflammation in AD. However, the roles of novel immunoregulatory cytokine IL-37 in basophils remain elusive. We employed in vitro co-culture of human basophils and human keratinocyte HaCaT cells and an in vivo MC903-induced AD murine model to investigate the anti-inflammatory mechanism of IL-37. In the in vitro model, IL-37b significantly decreased Der p1-induced thymic stromal lymphopoietin (TSLP) overexpression in HaCaT cells and decreased the expression of TSLP receptor as well as basophil activation marker CD203c on basophils. IL-37 could also reduce Th2 cytokine IL-4 release from TSLP-primed basophils ex vivo. In the in vivo model, alternative depletion of basophils ameliorated AD symptoms and significantly lowered the Th2 cell and eosinophil populations in the ear and spleen of the mice. Blocking TSLP alleviated the AD-like symptoms and reduced the infiltration of basophils in the spleen. In CRISPR/Cas9 human IL-37b knock-in mice or mice with direct treatment by human IL-37b antibody, AD symptoms including ear swelling and itching were significantly alleviated upon MC903 challenge. Notably, IL-37b presence significantly reduced the basophil infiltration in ear lesions. In summary, IL-37b could regulate the TSLP-mediated activation of basophils and reduce the release of IL-4. The results, therefore, suggest that IL-37 may target TSLP-primed basophils to alleviate AD.

• Authors: Tianheng Hou, Miranda Sin-Man Tsang, Lea Ling-Yu Kan, Peiting Li, Ida Miu-Ting Chu, Christopher Wai-Kei Lam, Chun-Kwok Wong
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 14 (Jul 09 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34299012 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• ENPP3 protein, human
• IL37 protein, human
• Interleukin-1
• Interleukin-4
• Phosphoric Diester Hydrolases
• Pyrophosphatases
• Thymic Stromal Lymphopoietin

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Basophils (drug effects, immunology)
• Cell Line
• Coculture Techniques
• Cytokines (antagonists & inhibitors, metabolism, pharmacology)
• Dermatitis, Atopic (drug therapy, genetics, immunology, metabolism)
• Down-Regulation
• Ear (pathology)
• Eosinophils (metabolism)
• Gene Knock-In Techniques
• Humans
• Interleukin-1 (genetics, metabolism, pharmacology, therapeutic use)
• Interleukin-4 (metabolism)
• Keratinocytes (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Phosphoric Diester Hydrolases (metabolism)
• Pyrophosphatases (metabolism)
• Spleen (immunology, metabolism)
• Th2 Cells (immunology)
• Up-Regulation
• Thymic Stromal Lymphopoietin