Activation and Control of CNS Innate Immune Responses in Health and Diseases: A Balancing Act Finely Tuned by Neuroimmune Regulators (NIReg)

Innate immunity is an arsenal of molecules and receptors expressed by professional phagocytes, glial cells and neurons and involved in host defence and clearance of toxic and dangerous cell debris. However, any uncontrolled innate immune responses within the central nervous system (CNS) are widely recognized as playing a major role in the development of autoimmune disorders and neurodegeneration, with multiple sclerosis (MS) and Alzheimer's diseases (AD) being primary examples. Critically, neuroimmune regulatory proteins (NIReg) may control the adverse immune responses in health and diseases. NIRegs are found mainly on neurons, glia, endothelia and ependymal cells and include GPI-anchored molecules (CD24, CD90, complement regulators CD55 and CD59), molecules of the immunoglobulin superfamily (siglec CD22, Siglec 10, CD200, ICAM-5) and others (CD47, fractalkine, TAM receptor tyrosine kinase and complement C3a and factor H). These regulators modulate the innate immune response in the CNS and for instance critically control the level of phagocytosis and inflammation engaged by resident microglia and infiltrating immune cells. Others will sequester and neutralize proinflammatory molecules such as HMGB1 and DNA. Moreover, some NIRegs can instigate the recruitment of stem cells to mediate tissue repair. In the absence of these regulators, when neurons die by apoptosis, become infected or damaged, microglia and infiltrating immune cells are free to cause injury and an adverse inflammatory response in acute and chronic settings. The therapeutic applications of NIRegs should be exploited given their natural and selective healing properties.

Mots clés

AIDS-Associated Dementia Alzheimer's Disease Apoptotic Atp B. Burgdorferi Cardif CD172a Cd200r Clec9A Cns Complement CpG DNA Bacteria Damp Danger Signals Drosophila Fibrinogen Fractalkine HLA Class I Ifnar innate immunity ITIMs LPS Bacteria Mavs Mincl Multiple Sclerosis MyD88 Necrotic Netrin NIReg N. Meningitidis Opsonin PAMPs Pathogen Phagocytosis Rage RNaseL Samp Semaphorin Tam Thrombin Visa Vitronectin Receptor

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Sciences du Vivant [q-bio]

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https://hal.univ-reunion.fr/hal-01274615

Soumis le : mardi 16 février 2016-08:42:39

Dernière modification le : jeudi 27 juin 2024-09:33:24

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hal-01274615 , version 1 (16-02-2016)

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HAL Id : hal-01274615 , version 1
DOI : 10.2174/187152711794488601

Citer

Jean-Jacques Hoarau, Pascale Krejbich-Trotot, Marie-Christine Jaffar-Bandjee, Trina Das, Gerard-Vincent Thon-Hon, et al.. Activation and Control of CNS Innate Immune Responses in Health and Diseases: A Balancing Act Finely Tuned by Neuroimmune Regulators (NIReg). Current Drug Targets -CNS and Neurological Disorders-, 2011, 10 (1), pp.25--43. ⟨10.2174/187152711794488601⟩. ⟨hal-01274615⟩

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