title: Aberrant Expression of Novel Cytokine IL-38 and Regulatory T Lymphocytes in Childhood Asthma.
abstract: We investigated the expression of novel anti-inflammatory interleukin (IL)-38 and regulatory T (Treg) lymphocytes in childhood asthma patients. The protein and mRNA expression level of IL-38, periostin, peripheral CD4⁺CD25⁺CD134⁺ T lymphocytes as well as CD4⁺CD25(high)FoxP3⁺ and CD4⁺CD25(high)CD127(-) Treg lymphocytes from 40 asthmatic patients and 20 normal control (NC) subjects were studied using ELISA, qPCR and flow cytometry. Serum and supernatant cytokines/chemokines were determined by multiplex assay. Serum IL-38, IL-5, IL-17, IL-6, interferon-γ, periostin, IL-1β and IL-13 concentrations were significantly higher in asthmatic patients with or without steroid treatment than those in controls (all p < 0.05). The percentages of both CD4⁺CD25(high)FoxP3⁺ and CD4⁺CD25(high)CD127(-) Treg lymphocytes were markedly decreased in asthmatic patients with and without steroid treatment than those in controls (all p < 0.05). The elevated IL-38 concentration negatively correlated with the percentage of Treg lymphocytes in asthmatic patients with high level (>40 ng/mL) of periostin (p < 0.05). Although the comparable mRNA levels of IL-38 and its receptor IL-36R were found between patients and controls, the mRNA level of IL-38 positively correlated with IL-36R and negatively correlated with IL-10 in all asthmatic patients (both p < 0.05). The percentage of CD4⁺CD25⁺CD134⁺ activated T lymphocytes was also significantly higher in asthmatic patients with steroid treatment than those in controls (p < 0.05). This cross-sectional study demonstrated that the overexpression of circulating IL-38 may play a role in the immunopathogenesis in asthma.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. shaanxichuman@gmail.com.|Shenzhen Research Institute, The Chinese University of Hong Kong, 518057 Shenzhen, China. shaanxichuman@gmail.com.
authors.forename: Man
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. idachu1219@gmail.com.|Shenzhen Research Institute, The Chinese University of Hong Kong, 518057 Shenzhen, China. idachu1219@gmail.com.
authors.forename: Ida M T
authors.initials: IM
authors.lastname: Chu
authors.affiliation: Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. eyung@cuhk.edu.hk.
authors.forename: Edmund C M
authors.initials: EC
authors.lastname: Yung
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China. wklam@must.edu.mo.
authors.forename: Christopher W K
authors.initials: CW
authors.lastname: Lam
authors.affiliation: Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. tfleung@cuhk.edu.hk.
authors.forename: Ting F
authors.initials: TF
authors.lastname: Leung
authors.affiliation: Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. wingkinwong@cuhk.edu.hk.
authors.forename: Gary W K
authors.initials: GW
authors.lastname: Wong
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. ck-wong@cuhk.edu.hk.|Shenzhen Research Institute, The Chinese University of Hong Kong, 518057 Shenzhen, China. ck-wong@cuhk.edu.hk.|Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China. ck-wong@cuhk.edu.hk.
authors.forename: Chun K
authors.initials: CK
authors.lastname: Wong
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D002648:Child; D005260:Female; D015870:Gene Expression; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D007378:Interleukins / Q000097:blood / Q000235:genetics*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000485:Allergens; D015415:Biomarkers; C571243:IL-38 protein, human; D007378:Interleukins; D012333:RNA, Messenger; D007073:Immunoglobulin E
keywords: IL-38; childhood asthma; cytokines; regulatory T lymphocytes