Both the brain and the immune system begin their journey with a learning process, directly linked to the environmental settings, to ultimately generate memory and execute effector functions; many of these functions control body homeostasis and are co-regulated throughout life. The implication of immune regulation in many disorders is thus a fast-emerging field as it holds a great promise in disease prevention, early diagnosis, and treatment.
Immune cell residence and function within the central nervous system
Immune cells begin to populate the central nervous system (CNS) already during embryonic development. The cells, termed microglia, become permanent residents of the tissue with a variety of functions such as clearance of pathogens and regulation of neuronal function. We address questions related to their unique differentiation process following entry into the CNS as well as their impact on chronic diseases of the brain such as epilepsy, multiple sclerosis and Alzheimer’s disease.
Immune mechanisms in aging and neurodegenerative diseases
Alzheimer’s disease is characterized by enhanced degeneration processes of the aging brain, which lead to cognitive decline and dementia. Our goal is to reveal immune mechanisms contributing to AD pathogenesis and thereby to develop immune-based early biomarkers and therapeutic approaches.
Mechanisms of stress-induced pathogenic autoimmunity and neuroinflammation
Chronic stress may alter the homeostatic functioning of the immune system by altering cellular responses to glucocorticoids. Such imbalance of immune regulation may then exacerbate or predispose to chronic illnesses such as depression, autoimmunity and neurodegenerative diseases. Our studies address the regulatory role of glucocorticoids in leukocyte and endothelial subsets and how such regulation is impaired following chronic stress or chronic inflammation.
3D scaffolds for immune modulation in autoimmune diseases
Although the etiology of autoimmune diseases is mostly unknown, it is becoming clear that a loss in immune regulation results in pathogenic stimulation of autoreactive lymphocytes which otherwise kept quiescent. Once such pathogenic stimulation of lymphocytes occurs, the cells can renew and continuously attack the body. Our research, in collaboration with Prof. Smadar Cohen, is aimed at generating transplantable lymphoid-like scaffolds which attenuate the function of pathogenic T cells and hence allow to preserve essential tissue functions.
Alon Monsonego, PhD
Professor, Lab of Neuroimmunology
Lawrence W. and Marie Feldman Chair in Neurophysiology
The Shraga Segal Dept. of Microbiology, Immunology and Genetics
The Faculty of Health Sciences &
The National Institute of Biotechnology in the Negev
Zlotowski Center for Neuroscience
Regenerative Medicine and Stem Cell Research Center
- Protein kinase C eta is activated in reactive astrocytes of an Alzheimer’s disease mouse model: Evidence for its immunoregulatory function in primary astrocytes.
Muraleedharan A., et al., Glia. 2020 Oct 17.
- Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes.
Elyahu Y., et al., Sci Adv. 2019 Aug 21;5(8):eaaw8330.
- CD4 T Cells Induce A Subset of MHCII-Expressing Microglia that Attenuates Alzheimer Pathology.
Mittal K., et al., iScience. 2019 Jun 28;16:298-311.
- BDNF-producing, amyloid β-specific CD4 T cells as targeted drug-delivery vehicles in Alzheimer’s disease.
- Eremenko E., et al., EBioMedicine. 2019 May;43:424-434.