title: Aberrant Expression of Bacterial Pattern Recognition Receptor NOD2 of Basophils and Microbicidal Peptides in Atopic Dermatitis.
abstract: Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease, associated with basophil infiltration into skin lesions and Staphylococcus aureus (S. aureus)-induced inflammation. Pattern recognition receptors (PRRs), including microbicidal peptide human neutrophil α-defensins (HNP) and dermcidin, can exert immunomodulating activity in innate immunity and skin inflammation. We investigated the plasma concentration of HNP and dermcidin, the expression of bacterial toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors of basophils and plasma concentration and ex vivo induction of AD-related inflammatory cytokines and chemokines using ELISA and flow cytometry, in AD patients and control subjects. Plasma concentrations of HNP, dermcidin and AD-related Th2 chemokines CCL17, CCL22 and CCL27 were significantly elevated in AD patients compared with controls (all p < 0.05). Plasma concentrations of CCL27 and CCL22 were found to correlate positively with SCORing atopic dermatitis (SCORAD), objective SCORAD, % area affected, lichenification and disease intensity, and CCL27 also correlated positively with pruritus in AD patients (all p < 0.05). Protein expressions of NOD2 but not TLR2 of basophils were significantly down-regulated in AD patients compared with controls (p = 0.001). Correspondingly, there were lower ex vivo % inductions of allergic inflammatory tumor necrosis factor-α, IL-6 and CXCL8 from peripheral blood mononuclear cells upon NOD2 ligand S. aureus derived muramyl dipeptide stimulation in AD patients comparing with controls. The aberrant activation of bacterial PRRs of basophils and anti-bacterial innate immune response should be related with the allergic inflammation of AD.
authors.affiliation: Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, 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-Kwok
authors.initials: CK
authors.lastname: Wong
authors.affiliation: Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. idachu1219@gmail.com.
authors.forename: Ida Miu-Ting
authors.initials: IM
authors.lastname: Chu
authors.affiliation: 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. ehon@cuhk.edu.hk.|Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. ehon@cuhk.edu.hk.
authors.forename: Kam-Lun
authors.initials: KL
authors.lastname: Hon
authors.affiliation: 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. tsangsinman0128@gmail.com.
authors.forename: Miranda Sin-Man
authors.initials: MS
authors.lastname: Tsang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. wklam@must.edu.mo.
authors.forename: Christopher Wai-Kei
authors.initials: CW
authors.lastname: Lam
mesh_terms: D000293:Adolescent; D001491:Basophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054422:Chemokine CCL22 / Q000097:blood; D054425:Chemokine CCL27 / Q000097:blood; D002648:Child; D023082:Defensins / Q000097:blood / Q000276:immunology; D003876:Dermatitis, Atopic / Q000097:blood* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000097:blood* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000097:blood*; D010455:Peptides / Q000097:blood / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity; D051195:Toll-Like Receptor 2 / Q000097:blood*
chemical_list: C515482:CCL22 protein, human; C492276:CCL27 protein, human; D054422:Chemokine CCL22; D054425:Chemokine CCL27; D023082:Defensins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D010455:Peptides; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C442243:dermcidin; C058181:insect defensin A
keywords: antimicrobial peptides; atopic dermatitis; basophils; chemokines; pattern recognition receptors