title: Histamine suppresses regulatory T cells mediated by TGF-β in murine chronic allergic contact dermatitis.
abstract: Regulatory T cells (Tregs) suppress effector T cells and ameliorate contact hypersensitivity (CH); however, the role of Tregs in chronic allergic contact dermatitis (CACD) has not been assessed. Repeated elicitation of CH has been used to produce CACD models in mice. We previously showed that the presence of histamine facilitates the creation of eczematous lesions in this model using histidine decarboxylase (HDC) (-/-) mice. Therefore, the effects of histamine on Tregs in the CACD model were investigated in this study. CACD was developed by repeated epicutaneous application of 2, 4, 6-trinitro-1-chlorobenzene (TNCB) on HDC (+/+) and HDC (-/-) murine skin to assess the effects of histamine in CACD. Histamine aggravated CACD in the murine model and suppressed the number of Tregs in the skin. Histamine also suppressed the level of TGF-β1 in this model. Recombinant TGF-β1 or anti-TGF-β1 antibody was injected into the dorsal dermis of HDC (+/+) mice daily just before TNCB challenge to determine the effects of histamine-regulated TGF-β on the Treg population in CACD. Recombinant TGF-β1 injection promoted the infiltration of Tregs in the skin and the production of IL-10; however, anti-TGF-β1 antibody injection suppressed the number of Tregs in the skin and the production of IL-10. Histamine suppresses the number of Tregs in CACD, and this effect is mediated by TGF-β.
authors: Department of Food and Nutrition Science, Sagami Women's Junior College, Bunkyo, Minamiku, Sagamihara, Kanagawa, Japan.
authors: Kyoko
authors: K
authors: Tamaka
authors: Masahiro
authors: M
authors: Seike
authors: Tamio
authors: T
authors: Hagiwara
authors: Atsushi
authors: A
authors: Sato
authors: Hiroshi
authors: H
authors: Ohtsu
mesh_terms: D000818:Animals; D002908:Chronic Disease; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006632:Histamine / Q000276:immunology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000172:deficiency / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010853:Picryl Chloride / Q000633:toxicity; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism
chemical_list: D006634:Histamine H1 Antagonists; C498829:Hrh4 protein, mouse; C556062:IL10 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D006632:Histamine; D006640:Histidine Decarboxylase; D010853:Picryl Chloride
keywords: TGF-β; chronic allergic contact dermatitis; histamine; regulatory T cell