16. Thymic Stromal Lymphopoietin

  1. Kenji Izuhara MD, PhD2,
  2. Stephen T. Holgate MD, DSc, FMedSci3 and
  3. Marsha Wills-Karp PhD4
  1. Kazuhiko Arima MD, PhD2 and
  2. Yong-Jun Liu MD, PhD1

Published Online: 27 JUL 2011

DOI: 10.1002/9781444346688.ch16

Inflammation and Allergy Drug Design

Inflammation and Allergy Drug Design

How to Cite

Arima, K. and Liu, Y.-J. (2011) Thymic Stromal Lymphopoietin, in Inflammation and Allergy Drug Design (eds K. Izuhara, S. T. Holgate and M. Wills-Karp), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444346688.ch16

Editor Information

  1. 2

    Department of Biomolecular Sciences, Division of Medical Biochemistry, Saga Medical School, Nabeshima, Saga, Japan

  2. 3

    School of Medicine, Allergy and Inflammation Research, Southampton General Hospital, University Medicine, Southampton, UK

  3. 4

    Division of Immunology, Cincinnati Children's Medical Center, Cincinnati, OH, USA

Author Information

  1. 1

    Department of Immunology, Center for Cancer Immunology Research, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA

  2. 2

    Department of Biomolecular Sciences, Division of Medical Biochemistry, Saga Medical School, Nabeshima, Saga, Japan

Publication History

  1. Published Online: 27 JUL 2011
  2. Published Print: 13 AUG 2011

ISBN Information

Print ISBN: 9781444330144

Online ISBN: 9781444346688

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Keywords:

  • thymic stromal lymphopoietin;
  • thymic stromal lymphopoietin (TSLP) - identified as lymphocyte growth, factor in mice;
  • constitutive and upregulated expression of TSLP - in multiple cell types, epithelial cells in allergic diseases;
  • TSLP receptor (TSLPR), a heterodimeric receptor complex - TSLPR and IL-7Rα chains;
  • TSLP and TSLP receptor - thymic stromal lymphopoietin, an interleukin 7 (IL-7)-like four-helix bundle cytokine;
  • TSLP in allergic inflammation - innate allergic immune responses, myeloid dendritic and natural killer T cells;
  • TSLP, triggering adaptive allergic immune responses - via mDCs TSLP, DCs inducing inflammatory T h2 cells;
  • intestinal parasite infection - and allergic Th2 responses, TSLP key role in protective Th2 immunity in gut;
  • TSLP signal transduction, in human primary mDCs - binding with TSLP receptor complex, generating intracellular signaling;
  • TSLP, and progress in pathogenesis of allergic inflammation - major cell type responsive to hTSLP, the mDC

Summary

Thymic stromal lymphopoietin (TSLP) has been recently implicated as a key molecule for initiating allergic inflammation at the epithelial cell–dendritic cell (DC) interface. In humans, TSLP is produced predominantly by epithelial cells and stimulates myeloid DCs (mDCs). TSLP-activated mDCs can promote the differentiation of naïve CD4+ T cells into a T helper 2 (Th2) phenotype, the expansion of CD4+ Th2 memory cells, as well as the induction of CD8+ proallergic cytotoxic T cells. Mouse genetic studies provide strong evidence for a pivotal role of TSLP in the pathogenesis of allergic diseases in vivo. Since TSLP is a rational therapeutic target for the treatment of allergic disorders, elucidating the mechanisms that regulate TSLP expression and the effects of TSLP on orchestrating the immune response toward a Th2 phenotype is essential for developing anti-TSLP therapy.