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Expression of Major Histocompatibility Complex Class I (MHC-I/HLA) and its receptor LilrB2 in brain tissue and primary cultures of human astrocytes

Grant number: 17/03619-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2018
Effective date (End): July 31, 2020
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Alexandre Leite Rodrigues de Oliveira
Grantee:Raffaela Silvestre Ignarro
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The Major Histocompatibility Complex Class I (MHCI), in addition to its classical role in the immune system, is also involved in the neuroplasticity and response of nerve tissue to injury. In fact, it has been shown that the refinement of neural connections between the retina and the lateral geniculate nucleus of the thalamus is impaired in mice with MHC deficient expression. In this context, supernumerary synapses hamper the primary processing of visual information. On the other hand, in our laboratory, we demonstrated a greater loss of synapses in lumbar spinal cord after sciatic nerve axotomy in adult mice that do not express MHCI. Such loss occurred predominantly in inhibitory synapses and resulted in deficient axonal regeneration. Thus, we believe that the expression of MHCI promotes plasticity in damaged motoneurons, optimizing the regenerative process. According to this hypothesis, further studies in which interferon beta was used to increase MHCI expression in mice after peripheral nerve damage, revealed more pronounced axonal growth and functional improvement. In addition, astrocytes have been shown to reduce MHCI expression by spinal motoneurons in amyotrophic lateral sclerosis, making the latter more susceptible to deleterious stimuli. Although there are data on the expression of MHCI and its receptors on murine nerve tissue, such expression in humans is not known in detail. Thus, in the present study, the basal protein expression of MHCI and its LILRB2 receptor in brain tissues and expression in human astrocytes in vitro, before and after exposure to IFN-beta, will be investigated. For this, human brain tissues and primary cultures derived from normal cerebral cortex (anterior pole of the temporal lobe), obtained during access to deep structures for the treatment of epileptic foci, will be used. The location and quantification of MHCI and LILRB2 will be assessed by immunofluorescence and co-localization assays. Furthermore, the important role of astrocytes in the immune system will be evaluated by studying the gene expression of anti-and proinflammatory cytokines in cultures before and after treatment with IFN-beta. In this context, the main objective of this work is to verify if human astrocytes express MHCI and LILRB2, molecules with potential neuroprotective action. In addition, we aim to initiate a new line of investigation in the Laboratory of Nerve Regeneration, studying the relationship between astrocytes and neurons after excitotoxic insults in vitro. (AU)