Treatment With CD52 Antibody Protects Neurons in Experimental Autoimmune Encephalomyelitis Mice During the Recovering Phase

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease driven by T and B lymphocytes. The remyelination failure and neurodegeneration results in permanent clinical disability in MS patients. A desirable therapy should not only modulate the immune system, but also promote neuroprotection and remyelination. To investigate the neuroprotective effect of CD52 antibody in MS, both C57BL/6J and SJL mice with experimental autoimmune encephalomyelitis (EAE) were treated with CD52 antibody at the peak of disease. Treatment with CD52 antibody depleted T but not B lymphocytes in the blood, reduced the infiltration of T lymphocytes and microglia/macrophages in the spinal cord. Anti-CD52 therapy attenuated EAE scores during the recovery phase. It protected neurons immediately after treatment (within 4 days) as shown by reducing the accumulation of amyloid precursor proteins. It potentially promoted remyelination as it increased the number of olig2/CC-1-positive mature oligodendrocytes and prevented myelin loss in the following days (e.g., 14 days post treatment). In further experiments, EAE mice with a conditional knockout of BDNF in neurons were administered with CD52 antibodies. Neuronal deficiency of BDNF attenuated the effect of anti-CD52 treatment on reducing EAE scores and inflammatory infiltration but did not affect anti-CD52 treatment-induced improvement of myelin coverage in the spinal cord. In summary, anti-CD52 therapy depletes CD4-positive T lymphocytes, prevents myelin loss and protects neurons in EAE mice. Neuronal BDNF regulates neuroprotective and anti-inflammatory effect of CD52 antibody in EAE mice.

Modulation of Alzheimer’s disease brain pathology in mice by gut bacterial depletion: the role of IL-17a

“…In additional experiments, we performed an immunohistochemical analysis of GFP in the brain of APP-transgenic mice and of EAE mice that were established in our previous study, 53 both of which expressed Il-17a-eGFP. We could not detect GFP-expressing cells in the brain parenchyma of AD mice, but clearly saw GFP-positive cells surrounding blood vessels in the EAE model (Supplementary Fig.…”

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

“…The abnormal expression of CCL18 [206], EOMES (eomesodermin) [207], GZMA (granzyme A) [208], HLA-DRB5 [209], GPNMB (glycoprotein nmb) [210], PRPH (peripherin) [211], HGF (hepatocyte growth factor) [212], TTR (transthyretin) [213], VEGFA (vascular endothelial growth factor A) [214], CHI3L1 [215], AATK (apoptosis associated tyrosine kinase) [216], SREBF1 [217], OLIG2 [218], ATF3 [219], NGFR (nerve growth factor receptor) [220], ADAMTS4 [221], LMNA (lamin A/C) [222], MT3 [223], DAO (D-amino acid oxidase) [224], AATK (apoptosis associated tyrosine kinase) [216] and LGALS3BP [225] might be related to the progression of amyotrophic lateral sclerosis. SLAMF7 [226], GPR174 [227], FCRL3 [228], SLAMF6 [229], EOMES (eomesodermin) [230], CCR4 [231], CCR2 [232], CD48 [233], CD3E [234], CCL26 [235], CCL4 [236], SLAMF1 [237], CD24 [238], IKZF3 [239], CD2 [240], CD28 [241], IL7R [242], FCGR2B [243], UBASH3A [244], CD1C [245], ICOS (inducible T cell costimulator) [246], CD3G [247], CCL3 [248], LTF (lactotransferrin) [249], GPNMB (glycoprotein nmb) [250], CTLA4 [251], IRF4 [252], TNFRSF9 [253], FCRL5 [254], LAIR2 [255], TAB2 [256], CD52 [257], CD163 [258], MSR1 [259], HGF (hepatocyte growth factor) [260], SIGLEC1 [261], TTR (transthyretin) [262], IL24 [263], IL9 [264], CHI3L1 [265], CDH1 [266], OLIG2 [267], NKX6-2 [268]. HK2 [269], PNPLA3 [270], CPB2 [271], SEMA4C [272], LRP2 [273], SLC5A11 [274], F11 […”

AhR Activation Leads to Attenuation of Murine Autoimmune Hepatitis: Single-Cell RNA-Seq Analysis Reveals Unique Immune Cell Phenotypes and Gene Expression Changes in the Liver

“…Cd52 was upregulated in the ConA alone group and downregulated in the ConA+TCDD group (Figure 6E). Antibodies against CD52 have been used to decrease the level of surface antigen and treat multiple sclerosis and its murine model experimental autoimmune encephalomyelitis (EAE) (33).…”