Reviews and feature article
Thymic stromal lymphopoietin and allergic disease

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The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways, and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies in both human subjects and murine models have implicated TSLP in the development and progression of allergic diseases. This review will highlight recent advances in the understanding of the role of TSLP in these inflammatory diseases. Importantly, these insights into TSLP's multifaceted role could potentially allow for novel therapeutic manipulations of these disorders.

Section snippets

TSLP biology

TSLP is a member of the 4-helix bundle cytokine family and a distant paralog of IL-7.6 Murine TSLP was discovered as an activity in the supernatants of a thymic stromal cell line capable of supporting immature B-cell proliferation and development.7, 8 Consistent with its similarity to IL-7, TSLP was shown to costimulate thymocyte proliferation and to promote B-cell lymphopoiesis.9, 10 Subsequently, a human homolog was identified by using in silico methods.11 Interestingly, human and murine TSLP

TSLP and allergic diseases

The first link of TSLP to allergic disease came from studies by Soumelis et al2 showing increased expression of TSLP in the lesional skin of patients with AD. Since then, numerous studies in both human subjects and mice have implicated TSLP in other atopic diseases, including asthma, AR, and food allergies.4, 5, 35 The following sections describe the disorders associated with TSLP and what is known about the mechanisms through which TSLP might act.

Clinical perspectives

Collectively, these data argue that the TSLP-TSLPR axis is an attractive therapeutic target for the treatment of allergic inflammatory diseases. Because it is aberrant expression of TSLP that is associated with human allergic disease, blockade of the receptor or neutralization of the cytokine is a logical starting point. In fact, phase II studies are underway using a fully humanized anti-TSLP antibody (AMG 157; Amgen, Thousand Oaks, Calif) with asthma as the indication. Other likely indications

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  • Cited by (0)

    Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, and William T. Shearer, MD, PhD

    Support was provided by grants AI068731, AR056113, AR055695, HL098067, HL102708, and AR059058 from the National Institutes of Health and a grant from the Asthma and Allergy Foundation of America.

    Disclosure of potential conflict of interest: S. F. Ziegler has received research support from the National Institutes of Health; has received lecture fees from the American Academy of Allergy, Asthma & Immunology; and has received travel support from the Federation of Clinical Immunology Societies.

    Terms in boldface and italics are defined in the glossary on page 846.

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