DC‐derived TSLP promotes Th2 polarization in LPS‐primed allergic airway inflammation

• Published in: European journal of immunology Vol. 42; no. 7; pp. 1735 - 1743
• Main Authors: Zhang, Yanlu, Zhou, Xueping, Zhou, Baohua
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.07.2012
• Subjects: Allergic airway inflammation; Animals; Asthma - immunology; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Cell Differentiation - immunology; Cell Polarity - immunology; Cytokines - immunology; Dendritic Cells - immunology; Eosinophilia - immunology; Lipopolysaccharides - immunology; Lung - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Ovalbumin - immunology; Specific Pathogen-Free Organisms; Th2; Th2 Cells - immunology; TSLP
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201142123

Thymic stromal lymphopoietin (TSLP) plays important roles in the pathogenesis of allergic diseases. Whether and how TSLP is involved in the initial priming of T helper type‐2 (Th2) differentiation against harmless antigen remains unclear. Using an intranasal sensitization protocol with OVA and LPS, we showed that TSLP signaling is required for low‐dose LPS‐induced Th2 inflammation, but not for high‐dose LPS‐induced Th1 immunity. We further demonstrated that low‐dose LPS‐activated bone marrow‐derived dendritic cells expressed relatively high Tslp but low Il12a, and were able to prime naïve DO11.10 T cells to differentiate into Th2 cells in a TSLP‐dependent manner. After transfer into wild‐type recipient mice, the low‐dose LPS‐activated OVA‐loaded dendritic cells (DCs) induced airway eosinophilia, but primed neutrophil‐dominated airway inflammation when TSLP‐deficient DCs were used. These studies demonstrate that TSLP released by DCs in response to a low concentration of LPS plays a role in priming Th2 differentiation and thus may serve as a polarizing third signal, in addition to antigen/MHC class II and co‐stimulatory factors, from antigen‐presenting DCs to direct effector T‐cell differentiation.