| First Author | Zhong J | Year | 2020 |
| Journal | J Neuroinflammation | Volume | 17 |
| Issue | 1 | Pages | 113 |
| PubMed ID | 32276661 | Mgi Jnum | J:302412 |
| Mgi Id | MGI:6508261 | Doi | 10.1186/s12974-020-01789-2 |
| Citation | Zhong J, et al. (2020) Independent and inter-dependent immunoregulatory effects of NCF1 and NOS2 in experimental autoimmune encephalomyelitis. J Neuroinflammation 17(1):113 |
| abstractText | BACKGROUND: Increasing evidence has suggested that a single nucleotide polymorphism in the Ncf1 gene is associated with experimental autoimmune encephalomyelitis (EAE). However, the mechanisms of NCF1-induced immunoregulatory effects remain poorly understood. In this study, we focus on NCF1 deficiency-mediated effects on EAE in NOS2 dependent and independent ways. METHODS: To determine the effects of NCF1 and NOS2 during EAE development, we have established recombinant mouse strains deficient at NCF1 and/or NOS2 in a crossbreeding system. Different strains allow us to examine the entire course of the disease in the Nos2-null mice bearing a Ncf1 gene that encodes a mutated NCF1, deficient in triggering oxidative burst, after immunization with recombinant myelin oligodendrocyte glycoprotein (MOG)79-96 peptides. The peptide-induced innate and adaptive immune responses were analyzed by flow cytometry. RESULTS: NCF1-deficient mice developed a reduced susceptibility to EAE, whereas NCF1-NOS2 double-deficient mice developed an enhanced EAE, as compared with NOS2-deficient mice. Flow cytometry analyses show that double deficiencies resulted in an increase of neutrophils in the spleen, accompanied with higher release of interleukin-1beta in neutrophils prior to EAE onset. The additional deficiency in NCF1 had no added effect on either interleukin-17 or interferon-gamma secretion of T cells during the priming phase. CONCLUSIONS: These studies show that NCF1 and NOS2 interact to regulate peptide-induced EAE. |
