DC‐derived TSLP promotes Th2 polarization in LPS‐primed allergic airway inflammation
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,...
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| Published in | European journal of immunology Vol. 42; no. 7; pp. 1735 - 1743 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
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Wiley Subscription Services, Inc
01.07.2012
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| Abstract | 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. |
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| AbstractList | Thymic stromal lymphopoietin (TSLP) plays important roles in the pathogenesis of allergic diseases. Whether and how TSLP is involved in the initial priming of 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 in a TSLP dependent manner. After transfer into wild type recipient mice, the low-dose LPS-activated OVA-loaded DC induced airway eosinophilia, but primed neutrophil-dominated airway inflammation when TSLP-deficient DC were used. These studies demonstrated that TSLP released by DC 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 II and costimulatory factors, from antigen presenting DC to direct effector T cell differentiation. 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. 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. [PUBLICATION ABSTRACT] 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 naive 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. |
| Author | Zhang, Yanlu Zhou, Baohua Zhou, Xueping |
| AuthorAffiliation | Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 Institute of Biotechnology, Zhejiang University, Hangzhou 310029, China Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202 |
| AuthorAffiliation_xml | – name: Institute of Biotechnology, Zhejiang University, Hangzhou 310029, China – name: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202 – name: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 |
| Author_xml | – sequence: 1 givenname: Yanlu surname: Zhang fullname: Zhang, Yanlu organization: Herman B Wells Center for Pediatric Research – sequence: 2 givenname: Xueping surname: Zhou fullname: Zhou, Xueping organization: Zhejiang University – sequence: 3 givenname: Baohua surname: Zhou fullname: Zhou, Baohua organization: Indiana University School of Medicine |
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| SubjectTerms | 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 |
| Title | DC‐derived TSLP promotes Th2 polarization in LPS‐primed allergic airway inflammation |
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