Role of the <i>TSLP</i> and its Receptor in the Treatment of Asthma

Abstract

Thymic stromal lymphopoietin (TSLP) is a crucial cytokine in initiating and regulating immune responses. Various cell types, including epithelial cells, fibroblasts, and dendritic cells, synthesize TSLP. TSLP activates dendritic cells, which subsequently promote the differentiation of T cells into T-helper 2 (T H 2) cells, a subset of T cells that produce cytokines involved in allergic responses. Genetic studies have linked TSLP to the development of asthma and other inflammatory disorders, indicating its importance in the pathogenesis of these diseases. Inhibiting the TSLP-TSLR axis has been suggested as a precision medicine strategy for treating several phenotypes and endotypes of asthma. Tezepelumab is a human monoclonal antibody that selectively binds to TSLP, thereby blocking its interaction with its heterodimeric receptor, reducing inflammation in the airways, and improving asthma symptoms.

Role of Thymic Stromal Lymphopoietin in the Pathophysiology of Asthma and Clinical and Biological Effects of Blockade With Tezepelumab

“…Although this was not the primary endpoint, the CASCADE study showed that patients who received tezepelumab 210 mg SC had a nominally significantly greater reduction in AHR to mannitol, as well as a numerically greater proportion of negative mannitol responders than the placebo group, even if this was not the main objective of the study [48]. Similarly, the UPSTREAM study showed a greater mean change in PD15 at 12 weeks of treatment with tezepelumab 700 mg IV compared with individuals receiving placebo; however, this difference was not statistically α-chain (IL-7Rα or CD127) [22,23] and activates JAK1 (via IL-7Rα) and JAK2 (via TSLPR) [24].…”

“…TSLP has a particularly relevant role in asthma, illustrated by the increased risk of developing the disease in carriers of specific TSLP genetic variants [25][26][27][28]. Similarly, individuals with asthma are characterized by higher expression of TSLP and its derived cytokines in the bronchial mucosa and bronchoalveolar lavage (BAL) fluid than controls [19][20][21][22][23][24][25][26][27][28][29]. TSLP has been shown to increase eosinophil counts in the blood and airway mucosa of persons with asthma as a result of IL-5 and IL-13 production from mast cells, CD34 + , and ILC2 [30,31] and to indirectly promote IgE release through downstream effects on B cells [24].…”