title: Impact of T-cell receptor Vbeta haplotypes on the development of dermatitis in DS-Nh mice: synergistic production of interleukin-13 caused by staphylococcal enterotoxin C and peptide glycans from Staphylococcus aureus.
abstract: Although the pathogenic role of interleukin-13 (IL-13) is a key for atopic dermatitis (AD), the mechanism of IL-13 production in AD remains unclear. To investigate the role of the T-cell receptor Vbeta (TCR Vbeta) haplotype in the development of dermatitis and the production of IL-13 in the naturally occurring dermatitis model by staphylococcal enterotoxin C (SEC)-producing Staphylococcus aureus, we raised DS-Nh mice harbouring the TCR Vbeta(a) haplotype with a central deletion in the TCRBV gene segments, including TCR Vbeta8S2. Observation and histopathological analysis of the two mouse substrains with spontaneous dermatitis indicated that later onset and weaker severity of AD-like dermatitis were identified in mice with TCR Vbeta(a) compared to those with TCR Vbeta(b). Immunohistochemical examination revealed the infiltration of a large number of CD4-bearing T cells in the skin lesions in mice with TCR Vbeta(b) but not in those with TCR Vbeta(a). Interestingly, much lower levels of serum IL-13 were detected in mice with the TCR Vbeta(a) than in those with the TCR Vbeta(b) haplotype. In vitro, synthetic ligands (Pam(2)CSK4) of toll-like receptor 2 (TLR2) synergistically produced IL-13 with SEC in splenocytes of mice with TCR Vbeta(b) but not of those with TCR Vbeta(a), and natural killer T cells were essential for this synergism. Our findings suggested that this TCR Vbeta-haplotype-dependent synergism with TLR2 plays an important role in the development of AD-like dermatitis in DS-Nh mice.
authors.affiliation: Shionogi Discovery Research Laboratories, Shionogi & Co. Ltd, Osaka, Japan. takeshi.yoshioka@shionogi.co.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Kinichi
authors.initials: K
authors.lastname: Imura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hikita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirasawa
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Sakata
authors.forename: Takaji
authors.initials: T
authors.lastname: Matsutani
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Horikawa
authors.forename: Akinori
authors.initials: A
authors.lastname: Arimura
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004768:Enterotoxins / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D018793:Interleukin-13 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010457:Peptidoglycan / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013211:Staphylococcus aureus; D018089:Superantigens / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology
chemical_list: D004768:Enterotoxins; D018793:Interleukin-13; D008024:Ligands; D010457:Peptidoglycan; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C034959:enterotoxin C, staphylococcal; D003094:Collagen