Laura Piccio, MD, PhD
Associate Professor of Neurology
Induction and regulation of adaptive autoimmune responses in Multiple Sclerosis Read More
|Lab Phone:||(314) 362-3293|
|Keywords:||Multiple Sclerosis, experimental autoimmune encephalomyelitis, animal models, flow cytometry|
Induction and regulation of adaptive autoimmune responses in Multiple Sclerosis
My research focuses on Multiple sclerosis (MS). MS is a complex disease of unknown etiology involving central nervous system (CNS) inflammation, demyelination, and axonal damage. MS is generally believed to be an autoimmune disease consisting in an adaptive immune response (T and/or B cell mediated) directed against CNS myelin components. My research investigates the role played by the immune system in MS pathogenesis and utilizes human specimens obtained from MS subjects as well as the most commonly used MS animal model, experimental autoimmune encephalomyelitis (EAE). My goals are to apply my basic research findings to the clinic. Currently, I focus on two major areas:
Several lines of evidence suggest that the innate immune system plays a critical role in the induction and regulation of adaptive autoimmune responses in MS, as well as in myelin and axonal damage within the CNS. Cells of the innate immune system include dendritic cells, macrophages and microglia. Relevance of these cells to MS relate to their functions as antigen presenting cells, producers of cytokines/chemokines, in the clearance of debris within the CNS, and perhaps perpetrators of damage to myelin and/or axons. In particular, we are studying the role of Triggering Receptor Expressed on Myeloid cells-2 (TREM-2), expressed on innate immune cells, in MS tissue and the EAE model. TREM-2 is emerging as an important negative regulator of inflammation. These studies are funded by the National Multiple Sclerosis Society (NMSS) and the Federazione Italiana Sclerosi Multipla (FISM). An important tool we are using to investigate the roles of innate immune cells in EAE is CNS imaging in vivo and ex vivo using two-photon microscopy.
A second area of interest of our lab is the study of the complex interplay between the immune system and metabolism. In fact, the white adipose tissue is no longer considered just a fat depot; it is known to be an active source of a variety of cytokines with differing functions, named “adipokines.” Adipokines not only regulate metabolic pathways, but can also regulate immune and inflammatory responses. Recently, we have shown that a regimen of calorie restriction (CR) ameliorates the EAE model. It is likely that this is a consequence of the numerous metabolic, hormonal and cytokine/adipokine changes induced by CR. Currently we are dissecting out the different pathways activated during CR to assess their importance in mediating the beneficial effects of this dietary regimen in EAE. The ultimate goal is to translate our results to humans.