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Cutting Edge: IL-23 Receptor GFP Reporter Mice Reveal Distinct Populations of IL-17-Producing Cells

Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
The Journal of Immunology (Impact Factor: 5.36). 06/2009; 182(10):5904-8. DOI: 10.4049/jimmunol.0900732
Source: PubMed

ABSTRACT IL-23, an IL-12 family member, has been implicated in the development of Th17 cells and the progression of autoimmune diseases. However, due to the lack of availability of sensitive Ab reagents specific for the IL-23 receptor (IL-23R), it has been difficult to characterize the cell types that express the IL-23R and are responsive to IL-23 in vivo. To address the role of IL-23 in vivo, we have generated a novel "knock-in" mouse in which we have replaced the intracellular domain of the IL-23R with the GFP. We show that in addition to Th17 cells, a subset of myeloid cells express IL-23R and respond to IL-23 by producing IL-17 and IL-22. Our studies further demonstrate that IL-23R expression is crucial for generation of encephalitogenic Th17 cells, but its expression on the innate immune system is dispensible in the development of experimental autoimmune encephalomyelitis.

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Available from: Caroline Pot, Jan 22, 2014
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    • "The IL-23p19 or IL-23R knockout mice were resistant to EAE. IL-23R is also expressed in the central nervous system by infiltrated macrophages, and macrophages expressing IL-23R in response to IL-17, IL-22, and IL-23 release (Awasthi et al., 2009; Cua et al., 2003; McGeachy et al., 2009). Therapeutic treatment with Anti-IL-23p19 can reduced the IL-17 serum level as well as mRNA expression of IL-6, IL-17, TNF, IFN-c, and Interferon gamma-induced protein-10 (IP-10) in central nervous system. "
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    • "C57BL/6J mice (#664), IL-12Rβ2−/− (#3248), RORγt−/− (#7572) and Rag1−/− (#2216) on C57BL/6 background were purchased from the Jackson Laboratory. IL-12Rβ2−/−, IL-23R-eGFP+/− and IL-23R-eGFP homozygous mice [16] (referred to in the text as IL-23R−/−) were maintained on a C57BL/6 background. IL-23R−/− and IL-12Rβ2−/− were bred to Rag1−/− to respectively generate IL-23R−/−.Rag1−/− and IL-12Rβ2−/−.Rag1−/− mice. "
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