Publications by authors named "Sandra Larouche"
Article Synopsis
- Multiple sclerosis (MS) is a complex disease involving immune cell infiltration into the central nervous system (CNS), but the exact mechanisms of this process are not well understood.
- This study used single-cell RNA sequencing and analyses of endothelial cells in an animal model of MS to uncover gene expression patterns related to neuroinflammation, particularly focusing on venous endothelial cells (ECs).
- Findings indicated that venous ECs play a significant role in neuroinflammation, with notable gene expression changes and molecular interactions identified, contributing to a better understanding of the processes that allow immune cells to enter the brain in MS.*
Article Synopsis
- The study investigates how autoreactive white blood cells, specifically CD4+ T lymphocytes, cross the blood-brain barrier, contributing to multiple sclerosis (MS) pathology.
- Researchers identified a protein called MCAM on brain endothelial cells that helps facilitate this migration of immune cells during neuroinflammation.
- Targeting MCAM could offer a new therapeutic strategy for treating MS by preventing the recruitment of these harmful T lymphocytes from the blood.
CLMP Promotes Leukocyte Migration Across Brain Barriers in Multiple Sclerosis.
Neurol Neuroimmunol Neuroinflamm
November 2022
Article Synopsis
- - The study investigates the role of coxsackie and adenovirus receptor-like membrane protein (CLMP) in the migration of immune cells into the central nervous system (CNS) of patients with multiple sclerosis (MS), focusing on how it contributes to CNS damage.
- - Researchers found that CLMP expression was significantly heightened in both the endothelial cells and immune cells of MS patients, particularly in active brain lesions, indicating its involvement in the inflammatory response associated with MS.
- - Blocking CLMP with specific antibodies reduced immune cell migration across brain endothelial cells in laboratory tests, suggesting that targeting CLMP may offer a potential therapeutic approach for managing MS-related inflammation.
The migration of circulating leukocytes into the central nervous system (CNS) is a key driver of multiple sclerosis (MS) pathogenesis. The monoclonal antibody natalizumab proved that pharmaceutically obstructing this process is an effective therapeutic approach for treating relapsing-remitting MS (RRMS). Unfortunately, the clinical efficacy of natalizumab is somewhat offset by its incapacity to control the progressive forms of MS (PMS) and by life-threatening side effects in RRMS rising from the expression of its molecular target, very late antigen 4 (VLA4), on most immune cells and consequent impairment of CNS immunosurveillance.
View Article and Find Full Text PDFInterleukin-26, preferentially produced by T17 lymphocytes, regulates CNS barrier function.
Neurol Neuroimmunol Neuroinflamm
November 2020
Objective: To investigate the involvement of interleukin (IL)-26 in neuroinflammatory processes in multiple sclerosis (MS), in particular in blood-brain barrier (BBB) integrity.
Methods: Expression of IL-26 was measured in serum, CSF, in vitro differentiated T helper (T) cell subsets, and postmortem brain tissue of patients with MS and controls by ELISA, quantitative PCR, and immunohistochemistry. Primary human and mouse BBB endothelial cells (ECs) were treated with IL-26 in vitro and assessed for BBB integrity.
The presence of B lymphocyte-associated oligoclonal immunoglobulins in the cerebrospinal fluid is a classic hallmark of multiple sclerosis (MS). The clinical efficacy of anti-CD20 therapies supports a major role for B lymphocytes in MS development. Although activated oligoclonal populations of pathogenic B lymphocytes are able to traffic between the peripheral circulation and the central nervous system (CNS) in patients with MS, molecular players involved in this migration have not yet been elucidated.
View Article and Find Full Text PDFArticle Synopsis
- TCR1640 mice are engineered to develop a condition similar to multiple sclerosis, showing different disease courses based on sex; females mostly experience a relapsing-remitting (RR) form while males tend to have a progressive form.
- Researchers conducted experiments transferring immune cells from both male and female TCR1640 mice into wild-type (WT) mice to see if the disease course is influenced by the donor's or recipient's sex.
- The study found that the female donor cells caused RR disease while male donor cells resulted in a progressive course, indicating that sex differences in gene expression among immune cells play a role in the type of neuroinflammatory disease observed.
Article Synopsis
- CD70 is a ligand for CD27 that is only expressed on activated immune cells, making its engagement crucial for immune responses.
- The upregulation of CD70 on CD4 T lymphocytes, induced by TGF-β1 and TGF-β3, enhances their ability to migrate into the central nervous system and promotes a pathogenic phenotype.
- CD70 is associated with T1 and T17 lymphocyte profiles, playing a significant role in T-bet and IFN-γ expression, and its presence in the CNS during autoimmune inflammation suggests it is a key immune marker and costimulator for pathogenic T lymphocytes.
Dual role of ALCAM in neuroinflammation and blood-brain barrier homeostasis.
Proc Natl Acad Sci U S A
January 2017
Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule found on blood-brain barrier endothelial cells (BBB-ECs) that was previously shown to be involved in leukocyte transmigration across the endothelium. In the present study, we found that ALCAM knockout (KO) mice developed a more severe myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). The exacerbated disease was associated with a significant increase in the number of CNS-infiltrating proinflammatory leukocytes compared with WT controls.
View Article and Find Full Text PDFBlood-brain barrier function is driven by the influence of astrocyte-secreted factors. During neuroinflammatory responses the blood-brain barrier is compromised resulting in central nervous system damage and exacerbated pathology. Here, we identified endothelial netrin 1 induction as a vascular response to astrocyte-derived sonic hedgehog that promotes autocrine barrier properties during homeostasis and increases with inflammation.
View Article and Find Full Text PDFEarly changes in the normal appearing white matter of multiple sclerosis (MS) patients precede the appearance of gadolinium-enhancing lesions. Although these findings suggest blood-brain barrier (BBB) breakdown as an important feature in MS pathogenesis, limited information is available on the BBB alterations during lesion genesis. Here, we perform a longitudinal characterization of the vascular, neuropathological and immunological changes before lesion formation in mice developing spontaneous relapsing-remitting experimental autoimmune encephalomyelitis (sRR-EAE).
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