Major histocompatibility complex class I-mediated inhibition of neurite outgrowth from peripheral nerves.
Studies of mice deficient in classical major histocompatability complex class I (MHCI) revealed that MHCI plays an important role in neurodevelopment in the central nervous system. We previously studied the effects of recombinant MHCI molecules on wildtype retina explants and observed that MHCI can inhibit retina neurite outgrowth, with self-MHCI molecules having greater inhibitory effect than non-self MHCI molecules. Here, we examined classical MHCI's effects on axon outgrowth from neurons of the peripheral nervous system (PNS). We used the embryonic dorsal root ganglia (DRG) explant model since their neurons express MHCI and because DRG explants have been widely used to assess the effects of molecules on axonal outgrowth from PNS neurons. We observed that picomolar levels of a recombinant self-MHCI molecule, but not non-self MHCI molecules, inhibited axon outgrowth from DRG explants. This differential sensitivity to self- vs. non-self MHCI suggests that early in development, self-MHCI may "educate" PNS neurons to express appropriate MHCI receptors, as occurs during natural killer cell development. Furthermore, we observed that a MHCI tetramer stained embryonic DRG neurons, indicating the expression of classical MHCI receptors. These results suggest that MHCI and MHCI receptors play roles during early stages of PNS development and may provide new targets of therapeutic strategies to promote neuronal outgrowth after PNS injury.
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90024, USA.
Zhongqi-Phyllis
ZP
Wu
Tina
T
Bilousova
Nathalie
N
Escande-Beillard
Hoa
H
Dang
Terry
T
Hsieh
Jide
J
Tian
Daniel L
DL
Kaufman
D000818:Animals; D001369:Axons / Q000276:immunology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000276:immunology / Q000378:metabolism; D005727:Ganglia, Spinal / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D016501:Neurites / Q000276:immunology* / Q000378:metabolism; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000276:immunology* / Q000378:metabolism
D015395:Histocompatibility Antigens Class I