Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma

Autor: Edwin Cheung, Christopher Wai-Kei Lam, Tiffany Nga-Teng Iu, Xiaoyu Sun, Victor Wai-Hou Tam, Chun-Kwok Wong, Ida Miu-Ting Chu, Miranda Sin-Man Tsang, Paul K.S. Chan, Tianheng Hou
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Chemokine
medicine.medical_treatment
Anti-Inflammatory Agents
Ligands
T-Lymphocytes
Regulatory
Mice
0302 clinical medicine
Immunology and Allergy
Cells
Cultured
Mice
Inbred BALB C
biology
medicine.diagnostic_test
Pyroglyphidae
respiratory system
Recombinant Proteins
Infectious Diseases
Cytokine
medicine.anatomical_structure
Cytokines
Inflammation Mediators
medicine.symptom
Injections
Intraperitoneal
Signal Transduction
Adult
Immunology
Down-Regulation
Bronchi
Inflammation
Models
Biological
Article
CCL5
Proinflammatory cytokine
03 medical and health sciences
Hypersensitivity
medicine
Animals
Humans
House dust mite
Tumor Necrosis Factor-alpha
business.industry
Interleukins
Epithelial Cells
Eosinophil
biology.organism_classification
Asthma
respiratory tract diseases
Eosinophils
Poly I-C
030104 developmental biology
Bronchoalveolar lavage
Gene Expression Regulation
biology.protein
business
030215 immunology
Zdroj: Cell Mol Immunol
ISSN: 2042-0226
1672-7681
DOI: 10.1038/s41423-019-0300-7
Popis: We elucidated the anti-inflammatory mechanisms of IL-38 in allergic asthma. Human bronchial epithelial cells and eosinophils were cocultured upon stimulation with the viral RLR ligand poly (I:C)/LyoVec or infection-related cytokine TNF-α to induce expression of cytokines/chemokines/adhesion molecules. House dust mite (HDM)-induced allergic asthma and humanized allergic asthma NOD/SCID murine models were established to assess anti-inflammatory mechanisms in vivo. IL-38 significantly inhibited induced proinflammatory IL-6, IL-1β, CCL5, and CXCL10 production, and antiviral interferon-β and intercellular adhesion molecule-1 expression in the coculture system. Mass cytometry and RNA-sequencing analysis revealed that IL-38 could antagonize the activation of the intracellular STAT1, STAT3, p38 MAPK, ERK1/2, and NF-κB pathways, and upregulate the expression of the host defense-related gene POU2AF1 and anti-allergic response gene RGS13. Intraperitoneal injection of IL-38 into HDM-induced allergic asthma mice could ameliorate airway hyperreactivity by decreasing the accumulation of eosinophils in the lungs and inhibiting the expression of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchoalveolar lavage fluid (BALF) and lung homogenates. Histological examination indicated lung inflammation was alleviated by reductions in cell infiltration and goblet cell hyperplasia, together with reduced Th2, Th17, and innate lymphoid type 2 cell numbers but increased proportions of regulatory T cells in the lungs, spleen, and lymph nodes. IL-38 administration suppressed airway hyperreactivity and asthma-related IL-4 and IL-5 expression in humanized mice, together with significantly decreased CCR3+ eosinophil numbers in the BALF and lungs, and a reduced percentage of human CD4+CRTH2+ Th2 cells in the lungs and mediastinal lymph nodes. Together, our results demonstrated the anti-inflammatory mechanisms of IL-38 and provided a basis for the development of a regulatory cytokine-based treatment for allergic asthma.
Databáze: OpenAIRE
Externí odkaz: