title: Impaired Toll-like receptor 2-mediated Th1 and Th17/22 cytokines secretion in human peripheral blood mononuclear cells from patients with atopic dermatitis.
abstract: BACKGROUND
  Impaired Toll-like receptor 2 (TLR2) function has been associated with the pathogenesis of atopic dermatitis (AD). However, there are only few studies reporting on the TLR2-induced immunological responses of circulating leucocytes of AD patients. We thus investigated the expression and secretion of Th1, Th2 and Th17/22 cytokines triggered by TLR2 ligands in human peripheral blood mononuclear cells (PBMCs) from AD patients. Expression of TLR2, 1, 6 and high-affinity receptor for IgE (FcεRI) were further investigated to evaluate the outcome of immune response in AD.
  
  
  METHODS
  Expression of TLR2, 1, 6 and FcεRI in PBMCs from AD patients and healthy individuals were measured by qPCR. Subsequent to stimulation with TLR2 ligands PGN and Pam3CSK4, expression and secretion of Th1, Th2 and Th17/22 cytokines were investigated by qPCR and ELISA.
  
  
  RESULTS
  The levels of TLR2, 1, 6 mRNA were not altered in both groups of subjects while that of FcεRI was increased in AD patients. Subsequent to the activation by TLR2 ligands, PBMCs from AD patients significantly released less IFN-γ, IL-17F and IL-22 than those from healthy controls while no detectable level of release was observed with the other cytokines. In contrast, significantly higher levels of mRNA expression for TNF-α, IL5, IL-17A and IL-22 were observed in TLR2 activated PBMCs of AD patients than those of healthy control.
  
  
  CONCLUSIONS
  PBMCs from AD patients are defective in the secretion of Th1 and Th17/22 cytokines in response to TLR2 ligands. The inconsistent increased expression of the mRNA for the corresponding Th1 cytokines and the Th2 cytokines IL-5 suggested that there may be alterations of downstream signaling events in the cytokine release mechanisms of PBMCs that are associated with the development of AD.
authors.affiliation: School of Medicine, Shenzhen University, Shenzhen, Guangdong, China. echoyyyu@163.com.|Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, No. 1120, Lianhua Road, Futian District, Shenzhen, 518036, Guangdong, China. echoyyyu@163.com.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, No. 1120, Lianhua Road, Futian District, Shenzhen, 518036, Guangdong, China. yinxiaolei_69@163.com.
authors.forename: Yarui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China. feelingzjzj@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China. douxia@medmail.com.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Dou
authors.affiliation: Department of Clinical Laboratory, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China. yhkrsy@yeah.net.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, No. 1120, Lianhua Road, Futian District, Shenzhen, 518036, Guangdong, China. shaoyong555@sina.com.|Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China. shaoyong555@sina.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, No. 1120, Lianhua Road, Futian District, Shenzhen, 518036, Guangdong, China. kepengwang@gmail.com.
authors.forename: Kepeng
authors.initials: K
authors.lastname: Wang
authors.affiliation: Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, No. 1120, Lianhua Road, Futian District, Shenzhen, 518036, Guangdong, China. yubomd@163.com.|Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China. yubomd@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, No. 1120, Lianhua Road, Futian District, Shenzhen, 518036, Guangdong, China. zhangweispace@yeah.net.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China. hyalau@cuhk.edu.hk.
authors.forename: Hang Yung Alaster
authors.initials: HY
authors.lastname: Lau
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009000:Monocytes / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism / Q000502:physiology*
chemical_list: D016207:Cytokines; D008024:Ligands; D051195:Toll-Like Receptor 2