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Investigation of the Role of CD4+ T cells and Interleukin‐10 in Immune‐Mediated Neuroprotection
Author(s) -
Olmstead Deborah,
Sanders Virginia,
Jones Kathryn
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.708.2
Subject(s) - microglia , axotomy , colocalization , neuroprotection , immune system , biology , in situ hybridization , microbiology and biotechnology , immunology , chemistry , inflammation , gene expression , regeneration (biology) , neuroscience , gene , biochemistry
Previous studies demonstrate that immunodeficient mice suffer significantly more motoneuron (MN) loss after facial nerve axotomy (FNA), and CD4+ T cells and interleukin‐10 (IL‐10) are the key mediators for MN survival. The objective of this study is to investigate the role of CD4+ T cells and IL‐10 in immune‐mediated neuroprotection. Our hypothesis is that the CD4+ T cells protect MN survival by regulating glial activation via microglia‐derived IL‐10. To study the role of CD4+ T cells, WT, immunodeficient RAG‐2 KO, and CD4+ T cell‐reconstituted RAG‐2 KO mice received a FNA, and qPCR analysis of the facial motor nucleus was conducted to compare gene expression profiles. Preliminary findings reveal that a robust MN regeneration response is present in all 3 groups. However, there is significant dysregulation in the glial response to FNA in the RAG‐2 KO mice compared to the WT and CD4+ reconstituted mice. These data suggest that CD4+ T cells regulate the glial response to injured MN, and this factor likely contributes to MN survival. To study the the role of IL‐10, mice expressing an IL‐10/GFP hybrid protein received a FNA, and immunohistochemistry was performed to identify colocalization of the IL‐10/GFP with microglia or astrocytes. The results demonstrate that microglia are the cellular source of IL‐10. In situ hybridization and qPCR of IL‐10 mRNA expression will also be performed. In summary, the current working hypothesis is that CD4+ T cells induce IL‐10 production in microglia which, in turn, regulates glial activation and creates an anti‐inflammatory environment that promotes MN survival after injury.