Faculty Opinions recommendation of Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated suppression of interleukin 17 receptor signaling.

2010 ◽  
Author(s):  
Noel Rose
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Interleukin 17 ◽  
Receptor Signaling ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated suppression of interleukin 17 receptor signaling

2010 ◽  
Vol 207 (12) ◽  
pp. 2647-2662 ◽  
Author(s):  
Shu Zhu ◽  
Wen Pan ◽  
Peiqing Shi ◽  
Hanchao Gao ◽  
Fang Zhao ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Cytokine ◽  
Inflammatory Responses ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 17 ◽  
Receptor Signaling ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Interleukin 17 (IL-17) plays critical roles in the pathogenesis of various autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE). How the signals triggered by this powerful inflammatory cytokine are controlled to avoid abnormal inflammatory responses is not well understood. In this study, we report that TRAF3 is a receptor proximal negative regulator of IL-17 receptor (IL-17R) signaling. TRAF3 greatly suppressed IL-17–induced NF-κB and mitogen-activated protein kinase activation and subsequent production of inflammatory cytokines and chemokines. Mechanistically, the binding of TRAF3 to IL-17R interfered with the formation of the receptor signaling activation complex IL-17R–Act1–TRAF6, resulting in suppression of downstream signaling. TRAF3 markedly inhibited IL-17–induced expression of inflammatory cytokine and chemokine genes in vivo and consequently delayed the onset and greatly reduced the incidence and severity of EAE. Thus, TRAF3 is a negative regulator of IL-17R proximal signaling.

scholarly journals Oestrogen modulates experimental autoimmune encephalomyelitis and interleukin-17 production via programmed death 1

Immunology ◽  
2009 ◽  
Vol 126 (3) ◽  
pp. 329-335 ◽  
Author(s):  
Chunhe Wang ◽  
Babak Dehghani ◽  
Yuexin Li ◽  
Laurie J. Kaler ◽  
Arthur A. Vandenbark ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Interleukin 17 ◽  
Autoimmune Encephalomyelitis ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Experimental Autoimmune

scholarly journals Baricitinib Ameliorates Experimental Autoimmune Encephalomyelitis by Modulating the Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Chun Dang ◽  
Yaoheng Lu ◽  
Xingyu Chen ◽  
Qian Li
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cells ◽  
Onset Time ◽  
Janus Kinase ◽  
Orphan Receptor ◽  
Interleukin 17 ◽  
Signal Transducer ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune ◽  
Stat Pathway

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) and a CD4+ T cell-mediated autoimmune disease. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is recognized as the major mechanism that regulates the differentiation and function of T helper (Th) 1 and Th17 cells, which are recognized as pivotal effector cells responsible for the development of EAE. We used baricitinib, a JAK 1/2 inhibitor, to investigate the therapeutic efficacy of inhibiting the JAK/STAT pathway in EAE mice. Our results showed that baricitinib significantly delayed the onset time, decreased the severity of clinical symptoms, shortened the duration of EAE, and alleviated demyelination and immune cell infiltration in the spinal cord. In addition, baricitinib treatment downregulated the proportion of interferon-γ+CD4+ Th1 and interleukin-17+CD4+ Th17 cells, decreased the levels of retinoic acid-related orphan receptor γ t and T-bet mRNA, inhibited lymphocyte proliferation, and decreased the expression of proinflammatory cytokines and chemokines in the spleen of mice with EAE. Furthermore, our results showed the role of baricitinib in suppressing the phosphorylation of STATs 1, 3, and 4 in the spleen of EAE mice. Therefore, our study demonstrates that baricitinib could potentially alleviate inflammation in mice with EAE and may be a promising candidate for treating MS.

Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis

2016 ◽  
Vol 7 (3) ◽  
pp. 363-373 ◽  
Author(s):  
S. Stanisavljević ◽  
J. Lukić ◽  
M. Momčilović ◽  
M. Miljković ◽  
B. Jevtić ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Lymphoid Tissue ◽  
Dark Agouti ◽  
Interleukin 17 ◽  
Mesenteric Lymph Nodes ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund’s adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer’s patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4+ T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.

scholarly journals Independent and inter-dependent immunoregulatory effects of NCF1 and NOS2 in experimental autoimmune encephalomyelitis

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Jianghong Zhong ◽  
Anthony C. Y. Yau ◽  
Rikard Holmdahl
Keyword(s):  
Flow Cytometry ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Interferon Γ ◽  
Mouse Strains ◽  
Interleukin 17 ◽  
Autoimmune Encephalomyelitis ◽  
Mediated Effects ◽  
Different Strains ◽  
Deficient Mice ◽  
Experimental Autoimmune

Abstract 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-1β in neutrophils prior to EAE onset. The additional deficiency in NCF1 had no added effect on either interleukin-17 or interferon-γ secretion of T cells during the priming phase. Conclusions These studies show that NCF1 and NOS2 interact to regulate peptide-induced EAE.

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