TSLP: A Key Regulator of Asthma Pathogenesis

Overview

Journal Drug Discov Today Dis Mech

Publisher Elsevier

Date 2013 Dec 19

PMID 24348685

Citations 28

Authors

Erin E West

Mohit Kashyap

Warren J Leonard

Affiliations

Soon will be listed here.

Abstract

Asthma is a complex disorder of the airways that is characterized by T helper type 2 (Th2) inflammation. The pleiotrophic cytokine TSLP has emerged as an important player involved in orchestrating the inflammation seen in asthma and other atopic diseases. Early research elucidated the role of TSLP on CD4 T cells, and recent work has revealed the impact of TSLP on multiple cell types. Furthermore, TSLP plays an important role in the sequential progression of atopic dermatitis to asthma, clarifying the key role of TSLP in the pathogenesis of asthma, a finding with therapeutic implications.

Citing Articles

Thymic Stromal Lymphopoietin and Tezepelumab in Airway Diseases: From Physiological Role to Target Therapy.

Bagnasco D, De Ferrari L, Bondi B, Candeliere M, Mincarini M, Riccio A Int J Mol Sci. 2024; 25(11).

PMID: 38892164 PMC: 11172531. DOI: 10.3390/ijms25115972.

Effects of biological therapies on patients with Type-2 high asthma and comorbid obesity.

Garg D, Que L, Ingram J Front Pharmacol. 2024; 14:1315540.

PMID: 38259298 PMC: 10800376. DOI: 10.3389/fphar.2023.1315540.

Personalized and Precision Medicine in Asthma and Eosinophilic Esophagitis: The Role of T2 Target Therapy.

Bagnasco D, Savarino E, Yacoub M, Braido F, Candeliere M, Giannini E Pharmaceutics. 2023; 15(9).

PMID: 37765327 PMC: 10536373. DOI: 10.3390/pharmaceutics15092359.

Modulation of Human Dendritic Cell Functions by Phosphodiesterase-4 Inhibitors: Potential Relevance for the Treatment of Respiratory Diseases.

Nguyen H, Tiberio L, Facchinetti F, Ripari G, Violi V, Villetti G Pharmaceutics. 2023; 15(9).

PMID: 37765223 PMC: 10535230. DOI: 10.3390/pharmaceutics15092254.

Root Extract Ameliorates Ovalbumin-Induced Airway Inflammation in a CARAS Mouse Model by Modulating the IL-33/TSLP/NF-κB Signaling Pathway.

Jin J, Fan Y, Nguyen T, Yu Z, Song C, Lee S Int J Mol Sci. 2023; 24(15).

PMID: 37569890 PMC: 10420321. DOI: 10.3390/ijms241512514.

References

Kool M, Willart M, van Nimwegen M, Bergen I, Pouliot P, Virchow J . An unexpected role for uric acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma. Immunity. 2011; 34(4):527-40. DOI: 10.1016/j.immuni.2011.03.015. View

Nguyen K, Vanichsarn C, Nadeau K . TSLP directly impairs pulmonary Treg function: association with aberrant tolerogenic immunity in asthmatic airway. Allergy Asthma Clin Immunol. 2010; 6(1):4. PMC: 3161393. DOI: 10.1186/1710-1492-6-4. View

Harada M, Hirota T, Jodo A, Hitomi Y, Sakashita M, Tsunoda T . Thymic stromal lymphopoietin gene promoter polymorphisms are associated with susceptibility to bronchial asthma. Am J Respir Cell Mol Biol. 2010; 44(6):787-93. PMC: 3159073. DOI: 10.1165/rcmb.2009-0418OC. View

Torgerson D, Ampleford E, Chiu G, Gauderman W, Gignoux C, Graves P . Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet. 2011; 43(9):887-92. PMC: 3445408. DOI: 10.1038/ng.888. View

Hirota T, Takahashi A, Kubo M, Tsunoda T, Tomita K, Doi S . Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nat Genet. 2011; 43(9):893-6. PMC: 4310726. DOI: 10.1038/ng.887. View

Demehri S, Morimoto M, Holtzman M, Kopan R . Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma. PLoS Biol. 2009; 7(5):e1000067. PMC: 2700555. DOI: 10.1371/journal.pbio.1000067. View

Baru A, Hartl A, Lahl K, Krishnaswamy J, Fehrenbach H, Yildirim A . Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation. Eur J Immunol. 2010; 40(8):2259-66. DOI: 10.1002/eji.200939972. View

Sokol C, Chu N, Yu S, Nish S, Laufer T, Medzhitov R . Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response. Nat Immunol. 2009; 10(7):713-20. PMC: 3252751. DOI: 10.1038/ni.1738. View

Redhu N, Gounni A . Function and mechanisms of TSLP/TSLPR complex in asthma and COPD. Clin Exp Allergy. 2011; 42(7):994-1005. DOI: 10.1111/j.1365-2222.2011.03919.x. View

10.

Hill D, Siracusa M, Abt M, Kim B, Kobuley D, Kubo M . Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med. 2012; 18(4):538-46. PMC: 3321082. DOI: 10.1038/nm.2657. View

11.

Soumelis V, Reche P, Kanzler H, Yuan W, Edward G, Homey B . Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol. 2002; 3(7):673-80. DOI: 10.1038/ni805. View

12.

Rochman I, Watanabe N, Arima K, Liu Y, Leonard W . Cutting edge: direct action of thymic stromal lymphopoietin on activated human CD4+ T cells. J Immunol. 2007; 178(11):6720-4. DOI: 10.4049/jimmunol.178.11.6720. View

13.

Wang Y, Angkasekwinai P, Lu N, Voo K, Arima K, Hanabuchi S . IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J Exp Med. 2007; 204(8):1837-47. PMC: 2118667. DOI: 10.1084/jem.20070406. View

14.

Holgate S . Innate and adaptive immune responses in asthma. Nat Med. 2012; 18(5):673-83. DOI: 10.1038/nm.2731. View

15.

Lei L, Zhang Y, Yao W, Kaplan M, Zhou B . Thymic stromal lymphopoietin interferes with airway tolerance by suppressing the generation of antigen-specific regulatory T cells. J Immunol. 2011; 186(4):2254-61. PMC: 3125594. DOI: 10.4049/jimmunol.1002503. View

16.

Rochman Y, Kashyap M, Robinson G, Sakamoto K, Gomez-Rodriguez J, Wagner K . Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases JAK1 and JAK2 reveals a key difference from IL-7-induced signaling. Proc Natl Acad Sci U S A. 2010; 107(45):19455-60. PMC: 2984176. DOI: 10.1073/pnas.1008271107. View

17.

Zhu Z, Oh M, Yu J, Liu Y, Zheng T . The Role of TSLP in IL-13-induced atopic march. Sci Rep. 2012; 1:23. PMC: 3251897. DOI: 10.1038/srep00023. View

18.

Halim T, Krauss R, Sun A, Takei F . Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation. Immunity. 2012; 36(3):451-63. DOI: 10.1016/j.immuni.2011.12.020. View

19.

Liu M, Rogers L, Cheng Q, Shao Y, Fernandez-Beros M, Hirschhorn J . Genetic variants of TSLP and asthma in an admixed urban population. PLoS One. 2011; 6(9):e25099. PMC: 3178593. DOI: 10.1371/journal.pone.0025099. View

20.

Beck L, Leung D . Allergen sensitization through the skin induces systemic allergic responses. J Allergy Clin Immunol. 2000; 106(5 Suppl):S258-63. DOI: 10.1067/mai.2000.110159. View