NDLI: Dual TCR expression biases lung inflammation in DO11.10 transgenic mice and promotes neutrophilia via microbiota-induced Th17 differentiation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Warnier, Guy Lemaire, Muriel M. de Heusch, Magali Uyttenhove, Catherine Van Snick, Jacques Dumoutier, Laure Renauld, Jean-Christophe Stevens, Monique
Description	Country affiliation: Belgium Author Affiliation: Lemaire MM ( Ludwig Institute for Cancer Research, Brussels Branch, B-1200 Brussels, Belgium.)
Abstract	A commonly used mouse model of asthma is based on i.p. sensitization to OVA together with aluminum hydroxide (alum). In wild-type BALB/c mice, subsequent aerosol challenge using this protein generates an eosinophilic inflammation associated with Th2 cytokine expression. By constrast, in DO11.10 mice, which are transgenic for an OVA-specific TCR, the same treatment fails to induce eosinophilia, but instead promotes lung neutrophilia. In this study, we show that this neutrophilic infiltration results from increased IL-17A and IL-17F production, whereas the eosinophilic response could be restored upon blockade of IFN-Î³, independently of the Th17 response. In addition, we identified a CD4(+) cell population specifically present in DO11.10 mice that mediates the same inflammatory response upon transfer into RAG2(-/-) mice. This population contained a significant proportion of cells expressing an additional endogenous TCR -chain and was not present in RAG2(-/-) DO11.10 mice, suggesting dual antigenic specificities. This particular cell population expressed markers of memory cells, secreted high levels of IL-17A, and other cytokines after short-term restimulation in vitro, and triggered a neutrophilic response in vivo upon OVA aerosol challenge. The relative numbers of these dual TCR lymphocytes increased with the age of the animals, and IL-17 production was abolished if mice were treated with large-spectrum antibiotics, suggesting that their differentiation depends on foreign Ags provided by gut microflora. Taken together, our data indicate that dual TCR expression biases the OVA-specific response in DO11.10 mice by inhibiting eosinophilic responses via IFN-Î³ and promoting a neutrophilic inflammation via microbiota-induced Th17 differentiation.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	187
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2011-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Differentiation Immunology Chemotaxis, Leukocyte Neutrophils Pneumonia Receptors, Antigen, T-cell Th17 Cells Adoptive Transfer Animals Cell Separation Flow Cytometry Interferon-gamma Biosynthesis Interleukin-17 Lymphocyte Activation Mice Mice, Transgenic Metabolism Microbiology Ovalbumin Reverse Transcriptase Polymerase Chain Reaction Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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