smotic pump containing clozapine N-oxide (CNO, 4 mg/ml in PBS, Enzo Life Sciences). CNO was infused for 14 days at a flow rate of 2 μg/h. We intravenously administered pertussis toxin (200 ng, List Biological Laboratories) immediately prior to and 48 h after cytokine injection. We assessed daily EAE clinical scores according to the following criteria1: 0, no clinical disease; 0.5, partial ... smotic pump containing clozapine N-oxide (CNO, 4 mg/ml in PBS, Enzo Life Sciences). CNO was infused for 14 days at a flow rate of 2 μg/h. We intravenously administered pertussis toxin (200 ng, List Biological Laboratories) immediately prior to and 48 h after cytokine injection. We assessed daily EAE clinical scores according to the following criteria1: 0, no clinical disease; 0.5, partial
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, leading to demyelination and axonal degeneration. Neuronal excitotoxity mediated by Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) results in neuronal damage in experimental autoimmune encephalitis (EAE), an animal model of MS. Here, we define a critical role of excitatory neurons in the pathogenesis of CD4+ lymphocyte accumulation in EAE. We silenced the activity of excitatory neurons in a mouse model of targeted EAE using inhibitory designer receptors exclusively activated by designer drugs (DREADD) under a CaMKIIα promoter. Neuronal silencing mitigated clinical disease scores in EAE, reduced the expression of c-fos, Tnfα, Ccl2, and Ccr2 mRNAs in targeted EAE lesions, and prevented the migration of CD4+ lymphocytes towards neurons. Ccl2 shRNA treatment of targeted EAE suppressed the migration of CD4+ lymphocytes and alleviated the motor deficits of EAE. Our findings indicate that neuronal activation in EAE promotes the migration of CCR2+ CD4+ lymphocytes and that neuronal silencing with an inhibitory DREADD alleviates clinical and molecular markers of disease. Neuronal CCL2 is thought to be involved in promoting lymphocytes migration.
Oral chitin treatment improved demyelination in murine autoimmune encephalomyelitis model by inhibition of inflammatory responses
Mami, S;Yeganeh, F;Salari, AA;Anissian, A;Azizi, M;Hajimollahoseini, M;
International Immunopharmacology84106536April 30, 2020
Product: Pertussis Toxin from B. pertussis, Lyophilized in Buffer
The mice also received intraperitoneal injections of 300 ng pertussis toxin in 100 µl PBS (List Biological Lab, Campbell, CA, USA) on days 0 and 2 and were monitored for disease activity that was scored every day until day 25
Briefly, mice were immunized subcutaneously with 250 μg of MOG35-55 (Pepceuticals, United Kingdom) emulsified in CFA (BD Difco, Germany) and received 400 ng pertussis toxin (PTx, List Biological Laboratories, Inc.) intraperitoneally at the time of immunization Cached
Malaria-071, a controlled human malaria infection trial, demonstrated that administration of three doses of RTS,S/AS01 malaria vaccine given at one-month intervals was inferior to a delayed fractional dose (DFD) schedule (62.5% vs 86.7% protection, respectively). To investigate the underlying immunologic mechanism, we analyzed the B and T peripheral follicular helper cell (pTfh) responses. Here, we show that protection in both study arms was associated with early induction of functional IL-21-secreting circumsporozoite (CSP)-specific pTfh cells, together with induction of CSP-specific memory B cell responses after the second dose that persisted after the third dose. Data integration of key immunologic measures identified a subset of non-protected individuals in the standard (STD) vaccine arm who lost prior protective B cell responses after receiving the third vaccine dose. We conclude that the DFD regimen favors persistence of functional B cells after the third dose.
CRISPR screen in regulatory T cells reveals modulators of Foxp3