Human TSLP and TLR3 ligands promote differentiation of Th17 cells with a central memory phenotype under Th2‐polarizing conditions
| Autor: | Takuji Akamatsu, Junya Tanaka, Tsutomu Chiba, Akiyoshi Nishio, Kazuyuki Saga, Masahiro Kido, Norihiko Watanabe |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Thymic stromal lymphopoietin Cellular differentiation Immunology Cell T cell differentiation CD11c Inflammation chemical and pharmacologic phenomena Biology Ligands Toll‐like receptor 3 ligand Thymic Stromal Lymphopoietin medicine Interleukin 23 Immunology and Allergy Humans Th17 cells Receptor double‐stranded RNA Interleukin-17 IL‐23 hemic and immune systems Cell Differentiation Dendritic Cells T-Lymphocytes Helper-Inducer Toll-Like Receptor 3 Original Articles: Editor's Choice: Basic Mechanisms in Allergic Disease Th2 cells medicine.anatomical_structure Phenotype TSLP TLR3 Cytokines medicine.symptom Immunologic Memory |
| Zdroj: | Clinical and Experimental Allergy |
| ISSN: | 1365-2222 0954-7894 |
| Popis: | Summary Background Human thymic stromal lymphopoietin (TSLP) is expressed in the human asthmatic lung and activates dendritic cells (DCs) to strongly induce proallergic T-helper type 2 (Th2) cell responses, suggesting that TSLP plays a critical role in the pathophysiology of human asthma. Th2 cells are predominantly involved in mild asthma, whereas a mixture of Th1 and Th2 cells with neutrophilic inflammation, probably induced by Th17, affects more severe asthmatic disease. Exacerbation of asthmatic inflammation is often triggered by airway-targeting RNA viral infection; virus-derived double-stranded RNA, Toll-like receptor (TLR)3 ligand, activates bronchial epithelial cells to produce pro-inflammatory mediators, including TSLP. Objective Because TSLPR-expressing DCs express TLR3, we examined how the relationship between TSLP and TLR3 ligand stimulation influences DC activation. Methods CD11c+DCs purified from adult peripheral blood were cultured in TLR ligands containing media with or without TSLP and then co-cultured with allogeneic naive CD4+T cells. Results CD11c+ DCs responded to a combination of TSLP and TLR3 ligand, poly(I : C), to up-regulate expression of the functional TSLP receptor and TLR3. Although TSLP alone did not induce IL-23 production by DCs, poly(I : C) alone primed DCs for the production of IL-23, and a combination of TSLP and poly(I : C) primed DCs for further production of IL-23. The addition of poly(I : C) did not inhibit TSLP-activated DCs to prime naive CD4+ T cells to differentiate into inflammatory Th2 cells. Furthermore, DCs activated by a combination of TSLP and poly(I : C) primed more naive CD4+ T cells to differentiate into Th17-cytokine–producing cells with a central memory T cell phenotype compared with DCs activated by poly(I : C) alone. Conclusions These results suggest that through DC activation, human TSLP and TLR3 ligands promote differentiation of Th17 cells with the central memory T cell phenotype under Th2-polarizing conditions. |
| Databáze: | OpenAIRE |
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