Current Allergy and Asthma Reports

, Volume 6, Issue 5, pp 372–376 | Cite as

Thymic stromal lymphopoietin: A potential therapeutic target for allergy and asthma



Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that has recently been implicated as central to the microenvironment and is permissive for the immunologic cascade that initiates and propagates allergic immune responses. In humans, TSLP is produced predominantly by epithelial cells and activated mast cells, and stimulates myeloid dendritic cells (mDC), which uniquely express the heterodimeric TSLP receptor. TSLP-activated mDC can promote naïve CD4+ T cells to differentiate into a Th2 phenotype and can promote the expansion of CD4+ Th2 memory cells. Recent evidence implicates TSLP as playing a pivotal role in the pathobiology of allergic asthma and atopic dermatitis. The potential for TSLP to provide a new therapeutic target for the treatment of allergic disorders is compelling, and elucidating the mechanisms that regulate TSLP expression and the effects of TSLP on orchestrating the immune response toward a Th2 phenotype should facilitate this quest.


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References and Recommended Reading

  1. 1.
    Liu YJ: Thymic stromal lymphopoietin: master switch for allergic inflammation. J Exp Med 2006, 203:269–273. This article provides an excellent up-to-date review.PubMedCrossRefGoogle Scholar
  2. 2.
    Sims JE, Williams DE, Morrissey PJ, et al.: Molecular cloning and biological characterization of a novel murine lymphoid growth factor. J Exp Med 2000, 192:671–680.PubMedCrossRefGoogle Scholar
  3. 3.
    Friend SL, Hosier S, Nelson A, et al.: A thymic stromal cell line supports in vitro development of surface IgM+ B cells and produces a novel growth factor affecting B and T lineage cells. Exp Hematol 1994, 22:321–328.PubMedGoogle Scholar
  4. 4.
    Pandey A, Ozaki K, Baumann H, et al.: Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat Immunol 2000, 1:59–64.PubMedCrossRefGoogle Scholar
  5. 5.
    Park LS, Martin U, Garka K, et al.: Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: formation of a functional heteromeric complex requires interleukin 7 receptor. J Exp Med 2000, 192:659–670.PubMedCrossRefGoogle Scholar
  6. 6.
    Fujio K, Nosaka T, Kojima T, et al.: Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain. Blood 2000, 95:2204–2210.PubMedGoogle Scholar
  7. 7.
    Hiroyama T, Iwama A, Morita Y, et al.: Molecular cloning and characterization of CRLM-2, a novel type I cytokine receptor preferentially expressed in hematopoietic cells. Biochem Biophys Res Commun 2000, 272:224–229.PubMedCrossRefGoogle Scholar
  8. 8.
    Reche PA, Soumelis V, Gorman DM, et al.: Human thymic stromal lymphopoietin preferentially stimulates myeloid cells. J Immunol 2001, 167:336–343.PubMedGoogle Scholar
  9. 9.
    Soumelis V, Reche PA, Kanzler H, et al.: Human epithelial cells trigger dendritic cell-mediated allergic inflammation by producing TSLP. Nat Immunol 2002, 3:673–680.PubMedCrossRefGoogle Scholar
  10. 10.
    Walley AJ, Wiltshire S, Ellis CM, et al.: Linkage and allelic association of chromosome 5 cytokine cluster genetic markers with atopy and asthma associated traits. Genomics 2001, 72:15–20.PubMedCrossRefGoogle Scholar
  11. 11.
    Sutherland GR, Baker E, Fernandez KE, et al.: The gene for human interleukin 7 (IL7) is at 8q12-13. Hum Genet 1989, 82:371–372.PubMedCrossRefGoogle Scholar
  12. 12.
    Watanabe N, Wang YH, Lee HK, et al.: Hassall’s corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 2005, 436:1181–1185. This is the seminal article on the role of TSLP in the thymus.PubMedCrossRefGoogle Scholar
  13. 13.
    Soumelis V, Liu YJ: Human thymic stromal lymphopoietin: a novel epithelial cell-derived cytokine and a potential key player in the induction of allergic inflammation. Springer Semin Immunopathol 2004, 25:325–333.PubMedCrossRefGoogle Scholar
  14. 14.
    Ito T, Wang YH, Duramad O, et al.: TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med 2005, 202:1213–1223. This article clarifies the key role of OX20 ligand in mDC activation of Th2 cells.PubMedCrossRefGoogle Scholar
  15. 15.
    Giliani S, Mori L, de Saint Basile G, et al.: Interleukin-7 receptor alpha (IL-7Ralpha) deficiency: cellular and molecular bases. Analysis of clinical, immunological, and molecular features in 16 novel patients. Immunol Rev 2005, 203:110–126.PubMedCrossRefGoogle Scholar
  16. 16.
    Murata T, Taguchi J, Puri RK, et al.: Sharing of receptor subunits and signal transduction pathway between the IL-4 and IL-13 receptor system. Int J Hematol 1999, 69:13–20.PubMedGoogle Scholar
  17. 17.
    Isaksen DE, Baumann H, Trobridge PA, et al.: Requirement for stat5 in thymic stromal lymphopoietin-mediated signal transduction. J Immunol 1999, 163:5971–5977.PubMedGoogle Scholar
  18. 18.
    Liu Y-J: A unified theory of central tolerance in the thymus. Trends Immunol 2006, 27:215–221.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhou B, Comeau MR, Smedt TD, et al.: Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat Immunol 2005, 6:1047–1053. This article demonstrates the role of TSLP in the pathogenesis of allergic asthma in a murine model.PubMedCrossRefGoogle Scholar
  20. 20.
    Al-Shami A, Spolski R, Kelly J, et al.: A role for TSLP in the development of inflammation in an asthma model. J Exp Med 2005, 202:829–839. This article demonstrates the role of TSLP in the pathogenesis of allergic asthma in a murine model.PubMedCrossRefGoogle Scholar
  21. 21.
    Yoo J, Omori M, Gyarmati D, et al.: Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J Exp Med 2005, 202:541–549. This article demonstrates the role of TSLP in the pathogenesis of atopic dermatitis in a murine model.PubMedCrossRefGoogle Scholar
  22. 22.
    Li M, Messaddeq N, Teletin M, et al.: Retinoid X receptor ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic stromal lymphopoietin. Proc Natl Acad Sci U S A 2005, 102:14795–14800. This article demonstrates the role of TSLP in the pathogenesis of atopic dermatitis in a murine model.PubMedCrossRefGoogle Scholar
  23. 23.
    Ying S, O’Connor B, Ratoff J, et al.: Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J Immunol 2005, 174:8183–8190. This article provides the first association of TSLP expression in the airways of asthmatic patients.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  1. 1.Immunology Allergy & Rheumatology SectionBaylor College of MedicineHoustonUSA

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