Publikationsdatenbank
MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4 (2015)
- Art
- Zeitschriftenartikel / wissenschaftlicher Beitrag
- Autoren
- Walsh, James T.
- Hendrix, Sven
- Boato, Francesco
- Smirnov, Igor
- Zheng, Jingjing
- Lukens, John R.
- Gadani, Sachin
- Hechler, Daniel
- Gölz, Greta (WE 8)
- Rosenberger, Karen
- Kammertöns, Thomas
- Vogt, Johannes
- Vogelaar, Christina
- Siffrin, Volker
- Radjavi, Ali
- Fernandez-Castaneda, Anthony
- Gaultier, Alban
- Gold, Ralf
- Kanneganti, Thirumala-Devi
- Nitsch, Robert
- Zipp, Frauke
- Kipnis, Jonathan
- Quelle
- The Journal of clinical investigation; 125(2) — S. 699–714
- ISSN: 0021-9738
- Sprache
- Englisch
- Verweise
- DOI: 10.1172/JCI76210
- Pubmed: 25607842
- Kontakt
- Institut für Lebensmittelsicherheit und -hygiene
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Königsweg 69
14163 Berlin
+49 30 838 62550
lebensmittelhygiene@vetmed.fu-berlin.de - Abstract / Zusammenfassung
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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.