title: Genetic variability in the rat Aplec C-type lectin gene cluster regulates lymphocyte trafficking and motor neuron survival after traumatic nerve root injury.
abstract: BACKGROUND
  C-type lectin (CLEC) receptors are important for initiating and shaping immune responses; however, their role in inflammatory reactions in the central nervous system after traumatic injuries is not known. The antigen-presenting lectin-like receptor gene complex (Aplec) contains a few CLEC genes, which differ genetically among inbred rat strains. It was originally thought to be a region that regulates susceptibility to autoimmune arthritis, autoimmune neuroinflammation and infection.
  
  
  METHODS
  The inbred rat strains DA and PVG differ substantially in degree of spinal cord motor neuron death following ventral root avulsion (VRA), which is a reproducible model of localized nerve root injury. A large F2 (DAxPVG) intercross was bred and genotyped after which global expressional profiling was performed on spinal cords from F2 rats subjected to VRA. A congenic strain, Aplec, created by transferring a small PVG segment containing only seven genes, all C-type lectins, ontoDA background, was used for further experiments together with the parental strains.
  
  
  RESULTS
  Global expressional profiling of F2 (DAxPVG) spinal cords after VRA and genome-wide eQTL mapping identified a strong cis-regulated difference in the expression of Clec4a3 (Dcir3), a C-type lectin gene that is a part of the Aplec cluster. Second, we demonstrate significantly improved motor neuron survival and also increased T-cell infiltration into the spinal cord of congenic rats carrying Aplec from PVG on DA background compared to the parental DA strain. In vitro studies demonstrate that the Aplec genes are expressed on microglia and upregulated upon inflammatory stimuli. However, there were no differences in expression of general microglial activation markers between Aplec and parental DA rats, suggesting that the Aplec genes are involved in the signaling events rather than the primary activation of microglia occurring upon nerve root injury.
  
  
  CONCLUSIONS
  In summary, we demonstrate that a genetic variation in Aplec occurring among inbred strains regulates both survival of axotomized motor neurons and the degree of lymphocyte infiltration. These results demonstrate a hitherto unknown role for CLECs for intercellular communication that occurs after damage to the nervous system, which is relevant for neuronal survival.
authors: Department of Clinical Neuroscience, Unit for Neuroimmunology, Karolinska Institutet, Stockholm, Sweden. rickard.lindblom@ki.se
authors: Rickard P F
authors: RP
authors: Lindblom
authors: Shahin
authors: S
authors: Aeinehband
authors: Roham
authors: R
authors: Parsa
authors: Mikael
authors: M
authors: Ström
authors: Faiez
authors: F
authors: Al Nimer
authors: Xing-Mei
authors: XM
authors: Zhang
authors: Cecilia A
authors: CA
authors: Dominguez
authors: Sevasti
authors: S
authors: Flytzani
authors: Margarita
authors: M
authors: Diez
authors: Fredrik
authors: F
authors: Piehl
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D017628:Microglia / Q000378:metabolism; D009046:Motor Neurons / Q000502:physiology*; D005810:Multigene Family / Q000235:genetics*; D009185:Myelin Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D011843:Radiculopathy / Q000235:genetics* / Q000473:pathology*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D013126:Spinal Nerve Roots / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D009185:Myelin Proteins; D000099192:CD69 Antigens
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