Commensal microbiota and its relationship to homeostasis and disease
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
Although one might intuitively anticipate that intestinal microbes exert influence over helper T-cell polarization in the gut, it is more surprising that gut microbes can modulate extraintestinal T-cell responses. Germ-free mice have impaired immunity and increased susceptibility to particular infections. However, they are also less sensitive to T-cell–mediated autoimmune conditions. Experimental allergic encephalomyelitis (EAE) is a frequently studied animal model of autoimmunity that mirrors aspects of human multiple sclerosis. Disease is mediated by T cells responding to antigens present on the myelin sheath that coats nerves. EAE can be induced in rodents and primates by immunization with nerve tissue–derived proteins or peptides, such as myelin basic protein or myelin oligodendrocyte glycoprotein in adjuvant. About 2 weeks after immunization, mice develop relapsing and remitting symptoms of weakness and paralysis. EAE is characterized by expansion of TH17 and TH1 cells in inflamed nerve tissue. It has been shown that germ-free mice are much less sensitive to EAE induction than mice colonized with a conventional intestinal microflora. Many germ-free mice failed to develop any neurologic features. EAE resistance in germ-free mice is associated with an attenuated inflammatory response. These experiments strongly implied that gut microbes are necessary for at least some pathogenic T-cell responses outside the gut (Figure 19.5).
Psychoneuroimmunology, Stress and Infection
Herman Friedman, Thomas W. Klein, Andrea L. Friedman in Psychoneuroimmunology, Stress, and Infection, 2020
Consistent with this, adrenal corticosteroids appear to play a critical role in recovery from experimental allergic encephalomyelitis (EAE). Rats treated with myelin basic protein produce antibodies to this protein 11–14 days after immunization, concurrently with paralysis of the tail and hind limbs and elevation of plasma corticosterone.55 Intact rats normally recover within a few days; the spontaneous recovery does not occur in adrenalectomized rats, unless glucocorticoid replacement therapy is instituted. Also, in Lewis rats, a decreased responsivity of the HPA axis is associated with the susceptibility to arthritis. Lewis rats show an arthritic response which mimics human rheumatoid arthritis in response to administration of a streptococcal cell wall peptidoglycan polysaccharide, whereas the histocompatible Fischer rats do not. The arthritic response in Lewis rats can be prevented by dexamethasone, and can be induced in Fischer rats by the glucocorticoid-receptor antagonist RU 486.77 The deficit in Lewis rats appears to be associated with a deficient activation of the HPA streptococcal cell wall peptidoglycan polysaccharide, IL-1, and CRF (compared to Fischer rats), and may be associated with an inappropriate regulation of the CRF gene. These two examples indicate a potential physiological significance for the glucocorticoid feedback on the immune response.
Use of Artemisia annua L. in the Treatment of Diseases—An Update
Tariq Aftab, M. Naeem, M. Masroor, A. Khan in Artemisia annua, 2017
Multiple sclerosis (MS) is a class of autoimmune disease that affects the central nervous system, and which is mediated by both T helper (Th) 17- and Th1-type cells. The main symptom of patients with MS is progressive paralysis. Experimental allergic encephalomyelitis (EAE) is a well-established murine model to study the pathogenesis of MS and also used for drug screening. In 2001, Zuo’ s group conducted an experiment to prove the immunosuppressive functions of novel artemisinin derivatives including SM735, SM905, and SM934 in vitro and in vivo . Later, Zhao et al. (2012) and Li et al. (2013) studied the immunosuppressive properties of SM933, another artemisinin derivative discovered by Zuo’ s group. It was established that SM933 exerted unique anti-inflammatory properties through regulatory mechanisms involving the NF-kB and Rig-G/JAB1 signaling pathways, leading to amelioration of EAE (Wang et al., 2007).
Prevention and treatment of experimental autoimmune encephalomyelitis induced mice with 1, 25-dihydroxyvitamin D3
Published in Neurological Research, 2019
Dariush Haghmorad, Esmaeil Yazdanpanah, Maryam Jadid Tavaf, Simin Zargarani, Azita Soltanmohammadi, Mohammad Bagher Mahmoudi, Mahmoud Mahmoudi
Experimental autoimmune encephalomyelitis (EAE) is an animal model for inflammatory disease of CNS, are considered being T helper-mediated autoimmune disease in which neural antigen-reactive lymphocytes infiltrate the CNS, leading to injury of axons and their myelin sheaths through a complex sequence of events [10]. EAE is largely employed as powerful tools to study the mechanisms of MS pathogenesis as well as a potential therapeutic intervention because it shares not only the pathological symptoms but also behavioral symptoms of MS [11]. EAE is thought to be initiated and driven by myelin-specific CD4+ T cells producing IFN-γ, TNF-α and IL-17 in the CNS while Th2 and Treg cells, producing anti-inflammatory cytokine such as IL-4, IL5 and TGF-β, IL-10, respectively, play a protective role against the progression of disease [12,13].
Novel nano-carriers with N-formylmethionyl-leucyl-phenylalanine-modified liposomes improve effects of C16-angiopoietin 1 in acute animal model of multiple sclerosis
Published in Drug Delivery, 2023
Xiao-Xiao Fu, Han Qu, Jing Wang, Hua-Ying Cai, Hong Jiang, Hao-Hao Chen, Shu Han
As a disease of the CNS caused by inflammatory demyelination, experimental allergic encephalomyelitis (EAE) shares many clinical and pathological features with MS, and is considered a model of MS (Arnon & Aharoni, 2009). A previous study has indicated that chemokines can induce inflammatory processes and demyelination in both EAE and MS (Karpus, 2020). Among the previously established rodent models of EAE, the acute model using Lewis rats has demonstrated a single peak of paralysis followed by spontaneous recovery, which is a characteristic of MS (Eng et al., 1996). This acute model can be helpful to elucidate the immune response in MS induced by inflammation and to study novel therapeutic agents. The inflammatory response in MS is complex, and suppressing the inflammation is a crucial goal when developing effective treatments (Han et al., 2013). Of the available anti-inflammatory drugs, glucocorticoids have shown central efficacy in MS (Eng et al., 1996). Unfortunately, this class of potent anti-inflammatory drugs, including methylprednisolone, gives rise to several undesirable side effects related to immunosuppression.
CD40 as a therapeutic target in Sjögren’s syndrome
Published in Expert Review of Clinical Immunology, 2018
Several studies have demonstrated prevention of autoimmunity initiation, slowing of autoimmune disease progression, reduced leukocytic infiltration, and end tissue damage through blockade of CD40L in murine models [3]. SLE, like pSS, is characterized by over-activation of both B and T cells. Anti-CD40L therapy has pronounced effects on B cell activation through sustained co-stimulatory blockade in murine models of lupus [10], and in lupus-prone mice, anti-CD40L treatment improved renal disease, and survival [6]. In experimental allergic encephalomyelitis, CD40L blockade reduced inflammation and tissue damage in brain tissue [3]. In mice with collagen-induced arthritis, anti-CD40L agent blocked joint inflammation development, production of anti-collagen antibodies, inflammatory cell infiltration in synovial tissue, and erosions of cartilage and bone [11].
Related Knowledge Centers
- Acute Disseminated Encephalomyelitis
- Central Nervous System
- Convalescence
- Demyelinating Disease
- Inflammation
- Myelin Basic Protein
- Virus
- Brain
- Multiple Sclerosis
- Myelin Proteolipid Protein