A soluble thymic stromal lymphopoietin (TSLP) antagonist, TSLPR-immunoglobulin, reduces the severity of allergic disease by regulating pulmonary dendritic cells.

Recent studies show that thymic stromal lymphopoietin (TSLP) plays a critical role in the upstream phase of the allergic cascade to induce T helper type 2 cell (Th2)-dominant allergic diseases. However, the effect of blocking TSLP signalling with the soluble TSLP receptor (TSLPR), TSLPR-immunoglobulin (Ig), on asthma development needs further investigation. Here, we examined the effects of TSLPR-Ig on asthmatic airway inflammation and dendritic cell (DC) function. TSLPR-Ig (comprising the extracellular domain of murine TSLPR and an IgG2a Fc tail) purified from transfected COS-7 cells reduced the expression of CD40, CD80 and CD86 on TSLP-activated DCs in vitro. We also investigated the mechanisms underlying TSLPR-Ig-mediated amelioration of allergic airway inflammation in a murine asthma model. When TSLP signalling was blocked by intratracheal administration of TSLPR-Ig prior to sensitization, allergen-specific serum IgE levels, airway tissue inflammation, inflammatory cell infiltration and Th2 cytokine levels in the bronchiolar lavage fluid (BALF) were reduced significantly. This was because of the TSLP-Ig-mediated down-regulation of co-stimulatory molecule expression on pulmonary DCs. We also transferred bone marrow-derived mature DCs (mDCs) into the airways of asthmatic mice. Intratracheal administration of TSLPR-Ig prior to the transfer of mDCs reduced eosinophilic airway inflammation and Th2 differentiation significantly. Collectively, these data suggest that local use of TSLPR-Ig prevents airway inflammation, at least in part, by regulating DC function, and that blocking TSLP signalling using TSLPR-Ig may be a novel strategy for the treatment of asthma bronchiale.

Zhang F ，Huang G ，Hu B ，Song Y ，Shi Y ... -  《-》

Blockage of thymic stromal lymphopoietin signaling improves acute lung injury in mice by regulating pulmonary dendritic cells.

Pan G ，Liang Y ，Lu L ，Chen X ，Wang M ，Wang L ，Yan C ，Zhang W ... -  《International Journal of Clinical and Experimental Pathology》

Thymic stromal lymphopoietin promotes lung inflammation through activation of dendritic cells.

Li YL ，Li HJ ，Ji F ，Zhang X ，Wang R ，Hao JQ ，Bi WX ，Dong L ... -  《-》

Thymic stromal lymphopoietin receptor blockade reduces allergic inflammation in a cynomolgus monkey model of asthma.

Cheng DT ，Ma C ，Niewoehner J ，Dahl M ，Tsai A ，Zhang J ，Gonsiorek W ，Apparsundaram S ，Pashine A ，Ravindran P ，Jung J ，Hang J ，Allard J ，Bitter H ，Tribouley C ，Narula S ，Wilson S ，Fuentes ME ... -  《-》

Local blockade of TSLP receptor alleviated allergic disease by regulating airway dendritic cells.

Shi L ，Leu SW ，Xu F ，Zhou X ，Yin H ，Cai L ，Zhang L ... -  《-》