Thymic Stromal Lymphopoietin

TSLP is an epithelial cytokine(alarmmin), a distant paralogue of interleukin-7 (IL7) that was originally detected in a mouse thymic stromal cell line. TLSP supports B cell growth and modulates thymocyte proliferation in vitro (Wang SH et al. 2021). Thymic stromal lymphopoietin (TSLP) is a key regulator of the immune system . It signals through a heterodimeric receptor complex (TSLPR) . This consists of the thymic stromal lymphopoietin receptor and an IL-7R-alpha chain. The 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 versch. Chemokines from monocytes and promotes the maturation of CD11c(+) dendritic cells. The cytokine promotes the response of T helper type 2 (TH2) cells, which are associated with immunity in various inflammatory diseases, including atopic dermatitis, food allergy, and asthma (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 allergic diseases (Ebina-Shibuya R et al. 2023).

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

In addition, lfTSLP is closely associated with skin fibrosis, epidermal hyperplasia, angiogenesis, and homeostatic tolerogenic regulations.

Although two isoforms (short and long form) of TSLP have been detected in human tissues, mainly the long form of TSLP (lfTSLP) plays an important role in the pathogenesis of allergy 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.

2021, a monoclonal antibody (tezepelumab) against TSLP was approved for the treatment of severe asthma 2021 for adults and children 12 years of age and older with uncontrolled severe asthma. Tezepelumab inhibits the action of thymic stromal lymphopoietin (TSLP). Blockade of TSLP is thought to prevent the release of proinflammatory cytokines by immune cells, which helps prevent asthma exacerbations and leads to improved asthma control. Tezepelumab has the potential to be effective in many patients with severe asthma, regardless of the type of inflammation, due to its target structure.

1. Ebina-Shibuya R et al (2023) Role of thymic stromal lymphopoietin in allergy and beyond. Nat Rev Immunol 23: 24-37.
2. Gauvreau GM et al (2020) Expert Opin Ther Targets PMID: 32567399 Review.
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. Zhou G et al (2023) Clinical trials of antibody drugs in the treatments of atopic dermatitis. Front Med (Lausanne) 10:1229539.

6. Ziegler SF et al (2013) The biology of thymic stromal lymphopoietin (TSLP). Adv Pharmacol 66:129-155.