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|Title: ||MHCII-independent CD4(+) T cells protect injured CNS neurons via IL-4|
|Authors: ||Walsh, James T.|
Lukens, John R.
|Issue Date: ||2015|
|Publisher: ||AMER SOC CLINICAL INVESTIGATION INC|
|Citation: ||JOURNAL OF CLINICAL INVESTIGATION, 125 (2), p. 699-714|
|Abstract: ||A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these,T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4(+) T cells from wild-type mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell-derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4-producing CD4(+) T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration.|
|Notes: ||Address correspondence to: Frauke Zipp, Neurology Department, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Phone: 0049.6131.17.2510; E-mail: Frauke.email@example.com. Or to: Jonathan Kipnis, Department of Neuroscience, University of Virginia, 409 Lane Rd., MR4, Charlottesville, Virginia 22908, USA. Phone: 434.982.3858; E-mail: firstname.lastname@example.org.|
|Link to publication: ||http://www.jci.org/articles/view/76210#sd|
|ISI #: ||000348962700026|
|Type: ||Journal Contribution|
|Validation: ||ecoom, 2016|
|Appears in Collections: ||Research publications|
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