TSLP gene

Thymic stromal lymphopoietin; Interleukin-7; CRSwNP; severe chronic rhinosinusitis with nasal polyps; skin fibrosis; epidermal hyperplasia; angiogenesis; tezepelumab; 

The TSLP gene (TSLP stands for: Thymic Stromal Lymphopoietin) is a protein coding gene located on chromosome 5q22.1. Alternative splicing of this gene results in several transcript variants.

The TSLP gene encodes a hematopoietic cytokine known as“thymic stromal lymphopoietin ( TSLP),” a distant paralog of interleukin-7 (IL-7). This is a pleiotropic molecule within the IL-2 family. TSLP was originally identified in mice in a thymic stromal cell line. TSLP supports the growth of B cells and modulates the proliferation of thymocytes in vitro (Wang SH et al. 2021).

Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine (alarmin) and a key regulator of the immune system. It signals via a heterodimeric receptor complex (TSLPR), which consists of the thymic stromal lymphopoietin receptor and an IL-7R-alpha chain.

Functional TSLPR is expressed by DCs, innate lymphoid cells (ILCs), mast cells, B cells, T cells, eosinophils, monocytes, and several non-hematopoietic cell populations, such as epithelial cells.

Thymic stromal lymphopoietin induces the release of various chemokines from monocytes and promotes the maturation of CD11c(+) dendritic cells. The cytokine promotes the response of type-2 T-helper cells (TH2), which are associated with immunity in various inflammatory diseases, including atopic dermatitis, food allergy, asthma, and chronic sinusitis with nasal polyps (Wang SH et al. 2021).

The protein is therefore considered a potential therapeutic target for the treatment of these diseases. It is best known for its role in promoting type 2 immune responses, such as those seen in allergic diseases (Ebina-Shibuya R et al. 2023).

However, it is now clear that TSLP has many other important functions in a variety of contexts. For example, several genetic variants of TSLP are associated with disease severity. Chromosomal alterations in TSLP are common in certain types of cancer, suggesting its important pathogenic role in these diseases.

Furthermore, the long form of TSLP (lfTSLP) is closely associated with skin fibrosis, epidermal hyperplasia, angiogenesis, and homeostatic tolerogenic mechanisms.

Although two isoforms (short and long forms) of TSLP have been detected in human tissue, the long form of TSLP (lfTSLP) in particular plays an important role in the pathogenesis of allergies and immune-mediated skin diseases (Wang SH et al. 2021).

The shorter (predominant) isoform is an antimicrobial protein that exhibits antibacterial and antifungal activity against B. cereus, E. coli, E. faecalis, S. mitis, S. epidermidis, and C. albicans. It is effective in the oral cavity and on the skin.

In 2021, tezeepelumab (^Tezspire®), a monoclonal antibody against TSLP, was approved for the treatment of severe asthma. ^Tezspire®may continue to be used (as of November 2025) as an add-on therapy to intranasal corticosteroid therapy in adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP).   

1. Ebina-Shibuya R et al (2023) Role of thymic stromal lymphopoietin in allergy and beyond. Nat Rev Immunol 23: 24-37.
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3. Roan F et al (2019) Epithelial cell-derived cytokines: more than an alarm signal. J Clin Invest 129:1441-1451.
4. Wang SH et al (2021) Thymic stromal lymphopoietin in cutaneous immune-mediated diseases. Front Immunol 12:698522.
5. Ziegler SF et al (2013) The biology of thymic stromal lymphopoietin (TSLP). Adv Pharmacol 66:129-155.
6. Zhou G et al (2023) Clinical trials of antibody drugs in the treatments of atopic dermatitis. Front Med (Lausanne) 10:1229539.