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

Korean Journal of Internal Medicine 2020년 35권 3호 p.619 ~ 629
이혜연 ( Lee Hea-Yon ) - Catholic University College of Medicine Department of Health Promotion Medicine

이화영 ( Lee Hwa-Young ) - Catholic University College of Medicine Department of Internal Medicine
 ( Hur Jung ) - Catholic University College of Medicine Department of Internal Medicine
강혜선 ( Kang Hye-Seon ) - Catholic University College of Medicine Department of Internal Medicine
최준영 ( Choi Joon-Young ) - Catholic University College of Medicine Department of Internal Medicine
이진국 ( Rhee Chin-Kook ) - Catholic University College of Medicine Department of Internal Medicine
강지영 ( Kang Ji-Young ) - Catholic University College of Medicine Department of Internal Medicine
김영균 ( Kim Young-Kyoon ) - Catholic University College of Medicine Department of Internal Medicine
이숙영 ( Lee Sook-Young ) - Catholic University College of Medicine Department of Internal Medicine

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 naive 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.

키워드

Asthma; Thymic stromal lymphopoietin; Airway resistance
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