Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 May 29;25(11):5972.
doi: 10.3390/ijms25115972.

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

Diego Bagnasco  1   2 , Laura De Ferrari  1   2 , Benedetta Bondi  1   2 , Maria Giulia Candeliere  1   2 , Marcello Mincarini  1   2 , Anna Maria Riccio  1   2 , Fulvio Braido  1   2
Affiliations
Review

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

Diego Bagnasco et al. Int J Mol Sci. .

Abstract

Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα. In recent years, the important role of proinflammatory cytokines in the etiopathogenesis of various chronic diseases such as asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), chronic obstructive pulmonary diseases (COPDs), and chronic spontaneous urticaria has been studied. Although alarmins have been found to be mainly implicated in the mechanisms of type 2 inflammation, studies on monoclonal antibodies against TSLP demonstrate partial efficacy even in patients whose inflammation is not definable as T2 and the so-called low T2. Tezepelumab is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating the safety and efficacy of Tezepelumab in various inflammatory disorders. In this review, we will highlight major recent advances in understanding the functional role of TSLP, its involvement in Th2-related diseases, and its suitability as a target for biological therapies.

Keywords: CRSwNP; T2 inflammation; TSLP; Tezepelumab; alarmins; cytokines; epithelium; mechanisms; severe asthma.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of key points in the production of thymic stromal lymphopoietin (TSLP), proinflammatory signaling by the ternary TSLP receptor-TSLP-Interleukin-7 Receptor alpha (TSLPR-TSLP-IL-7Rα) ternary complex and related effects on target cells.
Figure 2
Figure 2
Schematic representation of the Tezepelumab mechanism of action on blocking ternary TSLPR-TSLP-IL-7Rα complex formation and TSLP-related signaling.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Greenfeder S., Umland S.P., Cuss F.M., Chapman R.W., Egan R.W. Th2 Cytokines and Asthma—The Role of Interleukin-5 in Allergic Eosinophilic Disease. Respir. Res. 2001;2:71–79. doi: 10.1186/RR41. - DOI - PMC - PubMed
    1. Chan R., Stewart K., Misirovs R., Lipworth B.J. Targeting Downstream Type 2 Cytokines or Upstream Epithelial Alarmins for Severe Asthma. J. Allergy Clin. Immunol. Pract. 2022;10:1497–1505. doi: 10.1016/J.JAIP.2022.01.040. - DOI - PubMed
    1. Canè L., Poto R., Palestra F., Pirozzi M., Parashuraman S., Iacobucci I., Ferrara A.L., La Rocca A., Mercadante E., Pucci P., et al. TSLP is localized in and released from human lung macrophages activated by T2-high and T2-low stimuli: Relevance in asthma and COPD. Eur. J. Intern. Med. 2024. in press . - DOI - PubMed
    1. Hauser L.J., Chandra R.K., Li P., Turner J.H. Role of Tissue Eosinophils in Chronic Rhinosinusitis–Associated Olfactory Loss. Int. Forum Allergy Rhinol. 2017;7:957–962. doi: 10.1002/alr.21994. - DOI - PMC - PubMed
    1. Wang M., Bu X., Luan G., Lin L., Wang Y., Jin J., Zhang L., Wang C. Distinct Type 2-High Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma. Clin. Transl. Allergy. 2020;10:26. doi: 10.1186/s13601-020-00332-z. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources