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The Journal of Immunology, 2009, 182, 5904 -5908
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0900732

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Cutting Edge: IL-23 Receptor GFP Reporter Mice Reveal Distinct Populations of IL-17-Producing Cells1

Amit Awasthi2,*, Lorena Riol-Blanco2,*, Anneli Jäger2,{dagger}, Thomas Korn{ddagger}, Caroline Pot{dagger}, George Galileos*, Estelle Bettelli3,{dagger}, Vijay K. Kuchroo3,{dagger} and Mohamed Oukka3,*

* Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139; {dagger} Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; and {ddagger} Technische Universität München, Department of Neurology, Munich, Germany

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by grants from the National Institutes of Health (to M.O., E.B., and V.K.K.) and by National Multiple Sclerosis Society (NMSS) Grants RG-2571-D-9 (to V.K.K.) and RG-3882-A-1 (to M.O. and A.A.) and NMSS Transition Award TA 3014A1/1 (to E.B.). L.R.B. is supported by a postdoctoral fellowship from the European Molecular Biology Organization. A.J. is the recipient of a Ph.D. scholarship by the Boehringer Ingelheim Fonds. T.K. is supported by the Deutsche Forschungsgemeinschaft. C.P. is supported by the Swiss National Science Foundation.

2 A.A., L.R.-B., and A.J. contributed equally to this work.

3 Address correspondence and reprint requests to Dr. Mohamed Oukka, Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School 65 Landsdowne Street, Cambridge, MA 02139. E-mail address: moukka{at}rics.bwh.harvard.edu or Dr. Estelle Bettelli or Dr. Vijay K. Kuchroo, Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. E-mail addresses: ebettelli{at}rics.bwh.havard.edu and vkuchroo{at}rics.bwh.harvard.edu

4 Abbreviations used in this paper: WT, wild type; DC, dendritic cell; EAE, experimental autoimmune encephalomyelitis; ES, embryonic stem; LN, lymph node; LP, lamina propria; MOG, myelin oligodendrocyte glycoprotein.




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