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

Abstract	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.
Authors	F Zhang, G Huang, B Hu, Y Song, Y Shi
Journal	Clinical and experimental immunology (Clin Exp Immunol) Vol. 164 Issue 2 Pg. 256-64 (May 2011) ISSN: 1365-2249 [Electronic] England
PMID	21352203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.
Chemical References	B7-1 Antigen B7-2 Antigen CD40 Antigens Cd86 protein, mouse Immunoglobulins Receptors, Cytokine Recombinant Fusion Proteins Tslpr protein, mouse Immunoglobulin E Ovalbumin
Topics	Animals Asthma (drug therapy, immunology, pathology) B7-1 Antigen (biosynthesis, genetics) B7-2 Antigen (biosynthesis, genetics) CD40 Antigens (biosynthesis, genetics) COS Cells Chlorocebus aethiops Dendritic Cells (drug effects, immunology, transplantation) Disease Models, Animal Female Immunoglobulin E (blood) Immunoglobulins (genetics, therapeutic use) Lung (immunology, pathology) Mice Mice, Inbred BALB C Ovalbumin (immunology, toxicity) Protein Structure, Tertiary Receptors, Cytokine (genetics, therapeutic use) Recombinant Fusion Proteins (pharmacology, therapeutic use) Specific Pathogen-Free Organisms

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