EAE mediated by a non‐IFN‐γ/non‐IL‐17 pathway |
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| Authors: | Mark A Kroenke Stephen W Chensue Benjamin M Segal |
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| Institution: | 1. Holtom‐Garrett Program in Neuroimmunology, Department of Neurology, University of Michigan, Ann Arbor, MI, USA;2. Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA;3. Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA;4. Department of Pathology and Laboratory Medicine, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA |
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| Abstract: | Previous studies have shown that EAE can be elicited by the adoptive transfer of either IFN‐γ‐producing (Th1) or IL‐17‐producing (Th17) myelin‐specific CD4+ T‐cell lines. Paradoxically, mice deficient in either IFN‐γ or IL‐17 remain susceptible to EAE following immunization with myelin antigens in CFA. These observations raise questions about the redundancy of IFN‐γ and IL‐17 in autoimmune demyelinating disease mediated by a diverse, polyclonal population of autoreactive T cells. In this study, we show that an atypical form of EAE, induced in C57BL/6 mice by the adoptive transfer of IFN‐γ‐deficient effector T cells, required IL‐17 signaling for the development of brainstem infiltrates. In contrast, classical EAE, characterized by predominant spinal cord inflammation, occurred in the combined absence of IFN‐γ and IL‐17 signaling, but was dependent on GM‐CSF and CXCR2. Our findings contribute to a growing body of data, indicating that individual cytokines vary in their importance across different models of CNS autoimmunity. |
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| Keywords: | Autoimmunity EAE IL‐17 IFN‐γ MS |
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