TSLP Directly Interacts with Skin-Homing Th2 Cells Highly Expressing its Receptor to Enhance IL-4 Production in Atopic Dermatitis.
Thymic stromal lymphopoietin (TSLP) is overtly expressed on skin lesions of atopic dermatitis (AD), and the initiative role of TSLP-activated DCs in AD has gained much attention in the past few years, while its actions on other immune cells such as T cells have been given less notice. We aimed to clarify whether TSLP receptor (TSLPR) is expressed on certain populations of T cells and whether TSLP possesses the capability to directly interact with T cells from AD patients. Peripheral lymphocytes from 51 AD patients are analyzed by flow cytometry, and ex vivo experiments using peripheral blood and lesional skin-derived T cells were conducted. TSLPR expression was defined to CD4+ T cells, and CD4+CCR4+CXCR3-CCR7-CCR10+CLA+ T cells in AD patients exhibited enhanced TSLPR expression. The frequency of TSLPR+CD4+ T cells correlated with disease activity. CD4+ T cells from AD patients directly interacted with TSLP to produce a higher amount of IL-4 than those from normal subjects, and this action was attenuated with anti-TSLPR antibody. The importance of IL-4 in the induction of TSLPR expression was found in AD T cells. Our findings indicate that T cells from AD patients possess strong potential to directly interact with TSLP to promote Th2 response.
Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: ktat@hama-med.ac.jp.
Kazuki
K
Tatsuno
Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Toshiharu
T
Fujiyama
Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Hayato
H
Yamaguchi
Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Michihiko
M
Waki
Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yoshiki
Y
Tokura
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054414:Chemokine CCL17 / Q000097:blood; D016207:Cytokines / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007136:Immunoglobulins / Q000097:blood / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D054398:Receptors, CCR4 / Q000097:blood; D018121:Receptors, Cytokine / Q000097:blood / Q000502:physiology*; D012867:Skin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
C106230:CCL17 protein, human; C515354:CCR4 protein, human; D054414:Chemokine CCL17; D016207:Cytokines; C508598:IL4 protein, human; D007136:Immunoglobulins; D011948:Receptors, Antigen, T-Cell; D054398:Receptors, CCR4; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; D015847:Interleukin-4; D007073:Immunoglobulin E; D000094632:Thymic Stromal Lymphopoietin