TSLP Directly Interacts with Skin-Homing Th2 Cells Highly Expressing its Receptor to Enhance IL-4 Production in Atopic Dermatitis

J Invest Dermatol. 2015 Dec;135(12):3017-3024. doi: 10.1038/jid.2015.318. Epub 2015 Aug 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • Chemokine CCL17 / blood
  • Cytokines / physiology*
  • Dermatitis, Atopic / immunology*
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulins / blood
  • Immunoglobulins / physiology*
  • Interleukin-4 / biosynthesis*
  • Lymphocyte Activation
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, CCR4 / blood
  • Receptors, Cytokine / blood
  • Receptors, Cytokine / physiology*
  • Skin / immunology
  • Th2 Cells / immunology*
  • Thymic Stromal Lymphopoietin

Substances

  • CCL17 protein, human
  • CCR4 protein, human
  • Chemokine CCL17
  • Cytokines
  • IL4 protein, human
  • Immunoglobulins
  • Receptors, Antigen, T-Cell
  • Receptors, CCR4
  • Receptors, Cytokine
  • Tslpr protein, mouse
  • Interleukin-4
  • Immunoglobulin E
  • Thymic Stromal Lymphopoietin