Skip to main content

Advertisement

SpringerLink
Log in

Human thymic stromal lymphopoietin: a novel epithelial cell-derived cytokine and a potential key player in the induction of allergic inflammation

  • Original Paper
  • Published:
Springer Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Allergy is the result of a complex immune cascade leading to the dysregulated production of Th2 cytokines, the generation of allergen-specific IgE-producing B cells and the subsequent activation and degranulation of mast cells upon allergen challenge. Dendritic cells (DCs) play an important role in several models of allergy, but factors instructing DCs to induce a dysregulated Th2 response are currently unknown. In this review, we present recent evidence that human thymic stromal lymphopoietin (TSLP), a novel IL-7-like cytokine, might represent an early trigger of the allergic immune cascade. TSLP-activated human DCs produce Th2-attracting chemokines but no IL-12, and induce naive CD4+ and CD8+ T cell differentiation into effector cells with a typical pro-allergic phenotype. TSLP is produced by human epithelial, stromal, and mast cells. It is highly expressed by the keratinocytes of atopic dermatitis but not in other types of skin inflammation. Thus, epithelial- and stromal-cell-derived TSLP might represent one of the factors initiating the allergic responses, and could be a target for a curative therapeutic approach to allergy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Akbari O, DeKruyff RH, Umetsu DT (2001) Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2:725

  2. Akdis M, Simon HU, Weigl L, et al. (1999) Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8+ T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis. J Immunol 163:466

  3. Bertorelli G, Bocchino V, Zhou X, et al. (2000) Dendritic cell number is related to IL-4 expression in the airways of atopic asthmatic subjects. Allergy 55:449

  4. Bocchino V, Bertorelli G, Zhuo X, et al. (1997) Short-term treatment with a low dose of inhaled fluticasone propionate decreases the number of CD1a+ dendritic cells in asthmatic airways. Pulm Pharmacol Ther 10:253

  5. Borish L, Aarons A, Rumbyr TJ, et al. (1996) Interleukin-10 regulation in normal subjects and patients with asthma, J Allergy Clin Immunol 97:1288

  6. Busse WW, Rosenwasser LJ (2003) Mechanisms of asthma. J Allergy Clin Immunol 111:S799

  7. Carroll JM, Crompton T, Seery JP, et al. (1997) Transgenic mice expressing IFN-gamma in the epidermis have eczema, hair hypopigmentation, and hair loss. J Invest Dermatol 108:412

  8. Chomarat P, Banchereau J (1998) Interleukin-4 and interleukin-13: their similarities and discrepancies. Int Rev Immunol 17:1

  9. Corry DB (1999) IL-13 in allergy: home at last. Curr Opin Immunol 11:610

  10. Djukanovic R, Roche WR, Wilson JW, et al. (1990) Mucosal inflammation in asthma. Am Rev Respir Dis 142:434

  11. Fiorentino DF, Bond MW, Mosmann TR (1989) Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 170:2081

  12. Friend SL, Hosier S, Nelson A, et al. (1994) 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 22:321

  13. Fry TJ, Mackall CL (2002) Interleukin-7: from bench to clinic. Blood 99:3892

  14. Fujio K, Nosaka T, Kojima T, et al. (2000) Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain. Blood 95:2204

  15. Gilliet M, Soumelis V, Watanabe N, et al. (2003) Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells. J Exp Med 197:1059

  16. Greenfeder S, Umland SP, Cuss FM, et al. (2001) Th2 cytokines and asthma. The role of interleukin-5 in allergic eosinophilic disease. Respir Res 2:71

  17. Grewe M, Bruijnzeel-Koomen CA, Schopf E, et al. (1998) A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis. Immunol Today 19:359

  18. Grunig G, Warnock M, Wakil AE, et al. (1998) Requirement for IL-13 independently of IL-4 in experimental asthma. Science 282:2261

  19. Hamelmann E, Oshiba A, Paluh J, et al. (1996) Requirement for CD8+ T cells in the development of airway hyperresponsiveness in a marine model of airway sensitization. J Exp Med 183:1719

  20. Hessel EM, Van Oosterhout AJ, Van Ark I, et al. (1997) Development of airway hyperresponsiveness is dependent on interferon-gamma and independent of eosinophil infiltration. Am J Respir Cell Mol Biol 16:325

  21. Hiroyama T, Iwama A, Morita Y, et al. (2000) Molecular cloning and characterization of CRLM-2, a novel type I cytokine receptor preferentially expressed in hematopoietic cells. Biochem Biophys Res Commun 272:224

  22. Holgate ST (2000) The role of mast cells and basophils in inflammation. Clin Exp Allergy 30:28

  23. Holt PG, Macaubas C, Cooper D, et al. (1997) Th-1/Th-2 switch regulation in immune responses to inhaled antigens. Role of dendritic cells in the aetiology of allergic respiratory disease. Adv Exp Med Biol 417:301

  24. Kay AB (2001) Allergy and allergic diseases. Second of two parts. N Engl J Med 344:109

  25. Kupper TS (1990) The activated keratinocyte: a model for inducible cytokine production by non-bone marrow-derived cells in cutaneous inflammatory and immune responses. J Invest Dermatol 94:146S

  26. Lambrecht BN (2001) The dendritic cell in allergic airway diseases: a new player to the game. Clin Exp Allergy 31:206

  27. Lambrecht BN, De Veerman M, Coyle AJ, et al. (2000) Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J Clin Invest 106:551

  28. Lambrecht BN, Salomon B, Klatzmann D, et al. (1998) Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J Immunol 160:4090

  29. Levin SD, Koelling RM, Friend SL, et al. (1999) Thymic stromal lymphopoietin: a cytokine that promotes the development of IgM+ B cells in vitro and signals via a novel mechanism. J Immunol 162:677

  30. Li L, Xia Y, Nguyen A, et al. (1999) Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells. J Immunol 162:2477

  31. Lichtman AH, Abbas AK (1997) T-cell subsets: recruiting the right kind of help. Curr Biol 7:R242

  32. Moffatt MF, Cookson WO (1997) Tumour necrosis factor haplotypes and asthma. Hum Mol Genet 6:551

  33. Moller GM, Overbeek SE, Van Helden-Meeuwsen CG, et al. (1996) Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids. Clin Exp Allergy 26:517

  34. Moore KW, De Waal Malefyt R, Coffman RL, et al. (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683

  35. Nanavaty U, Goldstein AD, Levine SJ (2001) Polymorphisms in candidate asthma genes. Am J Med Sci 321:11

  36. Novak N, Haberstok J, Geiger E, et al. (1999) Dendritic cells in allergy. Allergy 54:792–803

  37. Nozaki S, Feliciani C, Sauder DN (1992) Keratinocyte cytokines. Adv Dermatol 7:83; discussion 101

  38. O’Garra A (1998) Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8:275

  39. Oh JW, Seroogy CM, Meyer EH, et al. (2002) CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation. J Allergy Clin Immunol 110:460

  40. O’Sullivan S, Cormican L, Faul JL, et al. (2001) Activated, cytotoxic CD8(+) T lymphocytes contribute to the pathology of asthma death. Am J Respir Crit Care Med 164:560

  41. Pandey A, Ozaki K, Baumann H, et al. (2000) Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat Immunol 1:59

  42. Park LS, Martin U, Garka K, et al. (2000) Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: formation of a functional heteromeric complex requires interleukin 7 receptor. J Exp Med 192:659

  43. Piguet PF (1992) Keratinocyte-derived tumor necrosis factor and the physiopathology of the skin. Springer Semin Immunopathol 13:345

  44. Quentmeier H, Drexler HG, Fleckenstein D, et al. (2001) Cloning of human thymic stromal lymphopoietin (TSLP) and signaling mechanisms leading to proliferation. Leukemia 15:1286

  45. Reche PA, Soumelis V, Gorman DM, et al. (2001) Human thymic stromal lymphopoietin preferentially stimulates myeloid cells. J Immunol 167:336

  46. Renauld JC (2001) New insights into the role of cytokines in asthma. J Clin Pathol 54:577

  47. Seneviratne SL, Jones L, King AS, et al. (2002) Allergen-specific CD8(+) T cells and atopic disease, J Clin Invest 110:1283

  48. Shah A, Church MK, Holgate ST (1995) Tumour necrosis factor alpha: a potential mediator of asthma. Clin Exp Allergy 25:1038

  49. Sims JE, Williams DE, Morrissey PJ, et al. (2000) Molecular cloning and biological characterization of a novel murine lymphoid growth factor. J Exp Med 192:671

  50. Soumelis V, Reche PA, Kanzler H, et al. (2002) Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol 3:673

  51. Stumbles PA (1999) Regulation of T helper cell differentiation by respiratory tract dendritic cells. Immunol Cell Biol 77:428

  52. Stumbles PA, Thomas JA, Pimm CL, et al. (1998) Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity. J Exp Med 188:2019

  53. Thepen T, Langeveld-Wildschut EG, Bihari IC, et al. (1996) Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH2 response to a TH1 response in situ: an immunocytochemical study. J Allergy Clin Immunol 97:828

  54. Werfel T, Morita A, Grewe M, et al. (1996) Allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in chronic skin lesions of atopic dermatitis. J Invest Dermatol 107:871

  55. Williams IR, Kupper TS (1996) Immunity at the surface: homeostatic mechanisms of the skin immune system. Life Sci 58:1485

  56. Yawalkar N, Schmid S, Braathen LR, et al. (2001) Perforin and granzyme B may contribute to skin inflammation in atopic dermatitis and psoriasis. Br J Dermatol 144:1133

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Necker Hospital, Paris, France

    Vassili Soumelis

  2. Department of Immunology, M.D. Anderson Cancer Center, Houston, Texas, USA

    Yong-Jun Liu

Authors
  1. Vassili Soumelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong-Jun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vassili Soumelis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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 Immun 25, 325–333 (2004). https://doi.org/10.1007/s00281-003-0152-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-003-0152-0

Keywords

Search

Navigation