Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma

Abstract

Background/Aims: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a key role in Th2-mediated inflammation, both directly by promoting the proliferation of naïve CD4 Th2 cells, and indirectly by activating dendritic cells (DCs). TSLP-activated DCs induce the expansion of chemoattractant receptor homologous molecule expressed on Th2 (CRTH2) + CD4 + Th2 memory cells, which undergo a Th2 response and express prostaglandin D2 (PGD2) synthase. CRTH2, a PGD2 receptor, is a selective Th2-cell surface marker. We investigated the effects of an anti-TSLP antibody (Ab) and a CRTH2 antagonist, as well as their mechanisms of action, in a mouse model of acute asthma. Methods: BALB/c mice were sensitized and challenged with ovalbumin. We then evaluated the effects of the administration of an anti-TSLP Ab either alone or together with a CRTH2 antagonist on cell counts, Th2 cytokine levels in bronchoalveolar fluid, and the levels of epithelium-derived cytokines such as TSLP, interleukin (IL) 33, and IL-25 in lung homogenates, as well as airway hyper-responsiveness (AHR). Results: Anti-TSLP Ab and the CRTH2 antagonist significantly attenuated eosinophilic airway inflammation, AHR, and the expression of Th2 cytokines. The expression of GATA-3 and the levels of IL-33 and IL-25 in lung tissues were affected by the combined anti-TSLP and CRTH2 antagonist treatment. Conclusions: These results suggest that the dual blockade of TSLP and CRTH2 may serve as an effective treatment target for eosinophilic asthma.

The impact of traditional mind–body exercises on pulmonary function, exercise capacity, and quality of life in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials

“…Traditional mind–body exercises can improve the quality of life of COPD patients for three main reasons: (1) The most fundamental pathophysiological change in COPD is obstructive ventilatory impairment, making pulmonary function a crucial factor influencing patient quality of life. Through traditional mind–body exercises and respiratory regulation, patients increase thoracic and lung activity, expand chest volume, promote alveolar expansion, improve respiratory muscle fatigue, and enhance pulmonary function, thus alleviating respiratory difficulties and improving quality of life ( 50 , 51 ). (2) Long-term engagement in traditional mind–body exercises significantly improves tension, anxiety, anger, hostility, fatigue, and other emotions in patients ( 52 ).…”

“…This scale tests COPD patients on items such as sputum, cough, sensations during stair climbing or uphill walking, chest tightness, confidence, household activities, energy, and sleep. It provides an assessment of patients' daily lives and physical and mental health, serving as an independent and comprehensive evaluation tool (49). Both the SGRQ and CAT scales are effective tools for assessing the health-related quality of life of stable COPD patients.…”

The role of peripheral type 2 innate lymphoid cells in bronchiolitis

“…TSLP regulates the differentiation of CD4 + naive T lymphocytes to Th2 cells by inducing dendritic cells to produce IL-4, IL-5, IL-13, etc. Animal experiments have found that the specific expression of TSLP can induce AHR, airway inflammation, goblet cell hyperplasia, and lack of TSLP cannot produce allergen-induced lung inflammatory response 26 , 27 . It is suggested that TSLP is involved in airway inflammatory diseases, which is in accordance with Liu’s research 28 .…”

Novel Anti-Cytokine Strategies for Prevention and Treatment of Respiratory Allergic Diseases

“…Targeting of alarmins proved beneficial as an add-on therapy or in combination with other cytokine inhibitors. Blockade of TSLP together with CRTH2, a chemoattractant receptor homologue expressed on Th2 memory cells, attenuated eosinophilic inflammation and AHR in ovalbumin-challenged mice ( 43 ). In line with this, bispecific anti-TSLP, anti-IL-13 reagent was recently developed in a form of monovalent antibody called Zweimab, and bivalent bispecific antibody scaffold – Doppelmab ( 44 ).…”