Experimental autoimmune neuritis

Fujioka, Toshiki

doi:10.1111/cen3.12461

Cited by 5 publications

(4 citation statements)

References 88 publications

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“…Furthermore, antibody treatment against IFN-γ or IFN-γR prevents renal disease in these mice ( Ozmen et al, 1995 ). With respect to the nervous system, it has been shown that loss of IFN-γR can reduce the autoimmune phenotype of experimental autoimmune neuritis, an animal model of the human Guillain–Barré syndrome, an autoimmune disorder of the peripheral nervous system ( Fujioka, 2018 ; Zhu et al, 1994 ; Hartung et al, 1990 ). Experimental autoimmune neuritis has been predominantly investigated in rats and can be induced with peripheral myelin antigens in combination with adjuvants, which causes CD4 T cell–mediated demyelination in the peripheral nervous system ( Zhu et al, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

Loss of direct adrenergic innervation after peripheral nerve injury causes lymph node expansion through IFN-γ

Chen¹,

Weber²,

Holtkamp³

et al. 2021

Journal of Experimental Medicine

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Peripheral nerve injury can cause debilitating disease and immune cell–mediated destruction of the affected nerve. While the focus has been on the nerve-regenerative response, the effect of loss of innervation on lymph node function is unclear. Here, we show that the popliteal lymph node (popLN) receives direct neural input from the sciatic nerve and that sciatic denervation causes lymph node expansion. Loss of sympathetic, adrenergic tone induces the expression of IFN-γ in LN CD8 T cells, which is responsible for LN expansion. Surgery-induced IFN-γ expression and expansion can be rescued by β2 adrenergic receptor agonists but not sensory nerve agonists. These data demonstrate the mechanisms governing the pro-inflammatory effect of loss of direct adrenergic input on lymph node function.

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Section: Discussionmentioning

confidence: 99%

Loss of direct adrenergic innervation after peripheral nerve injury causes lymph node expansion through IFN-γ

Chen¹,

Weber²,

Holtkamp³

et al. 2021

Journal of Experimental Medicine

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“…Experimental autoimmune neuritis (EAN) has been used as an animal model of human autoimmune-mediated peripheral neuritis in the development of therapies [ 8 ]. Interferon-gamma (IFN-γ)-producing autoreactive T lymphocytes induce EAN through the migration of macrophages from lymph nodes (LN) to immune-target organs, such as the peripheral nerves.…”

Section: Introductionmentioning

confidence: 99%

“…Macrophages are the final effector cells involved in the mechanism of demyelination in CIDP [ 9 ]. EAN also has multifocal and often perivascular mononuclear cell infiltration, which involves, lymphocytes and peripheral nerve demyelination by macrophages [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Siponimod ameliorates experimental autoimmune neuritis

Uchi

Konno

Kihara

et al. 2023

J Neuroinflammation

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Background Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are human autoimmune peripheral neuropathy. Besides humoral immunity, cellular immunity is also believed to contribute to these pathologies, especially CIDP. Sphingosine-1-phosphate receptor 1 (S1PR1) regulates the maturation, migration, and trafficking of lymphocytes. As of date, the therapeutic effect of sphingosine-1-phosphate receptor (S1PR) agonists on patients with GBS or CIDP remains unclear. Methods To evaluate the effect of siponimod, an agonist of S1PR1 and S1PR5, on experimental autoimmune neuritis (EAN), an animal model of autoimmune peripheral neuropathy, was used. Lewis rats were immunized with 125 μg of synthetic peptide from bovine P2 protein. Rats in the siponimod group were orally administered 1.0 mg/kg siponimod and those in the EAN group were administrated the vehicle on days 5–27 post-immunization (p.i.) daily. The symptom severity was recorded daily. The changes in the expression of cytokines and transcription factors in the lymph nodes and cauda equina (CE) which correlate with the pathogenesis of EAN and recovery of injured nerve were measured using reverse transcription quantitative PCR. Histological study of CE was also performed. Results Flaccid paralysis developed on day 11 p.i. in both groups. Siponimod relieved the symptom severity and decreased the expression of interferon-gamma and IL-10 mRNAs in lymph nodes and CE compared with that in the EAN group. The expression of Jun proto-oncogene (c-Jun) mRNA increased from the peak to the recovery phase and that of Sonic hedgehog signaling molecule (Shh) and Glial cell line-derived neurotrophic factor (Gdnf) increased prior to increase in c-Jun with no difference observed between the two groups. Histologically, siponimod also reduced demyelinating lesions and inflammatory cell invasion in CE. Conclusions Siponimod has a potential to ameliorate EAN. Shh and Gdnf, as well as C-Jun played a significant role during the recovery of injured nerves.

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“…In terms of primary demyelination, demyelinating EAN sensitized with myelin components should be reconsidered in research on AIDP, and ingenuity is required regarding antigens, appropriate animal species with genetic modulation, detection of shared biomarkers in AIDP and EAN, and exploration of new therapeutic agents. In this issue, Fujioka reviews the development of EAN and potential therapeutic approaches that provide a new perspective on the study of AIDP …”

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confidence: 99%