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Cells 2018, 7(9), 119; https://doi.org/10.3390/cells7090119

The Dual Immunoregulatory function of Nlrp12 in T Cell-Mediated Immune Response: Lessons from Experimental Autoimmune Encephalomyelitis

Program of Immunology, Department of Pediatrics, CR-CHUS, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
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Received: 3 August 2018 / Revised: 22 August 2018 / Accepted: 23 August 2018 / Published: 27 August 2018
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Abstract

Although the etiology of multiple sclerosis (MS) remains enigmatic, the role of T cells is unquestionably central in this pathology. Immune cells respond to pathogens and danger signals via pattern-recognition receptors (PRR). Several reports implicate Nlrp12, an intracellular PRR, in the development of a mouse MS-like disease, called Experimental Autoimmune Encephalomyelitis (EAE). In this study, we used induced and spontaneous models of EAE, as well as in vitro T cell assays, to test the hypothesis that Nlrp12 inhibits Th1 response and prevents T-cell mediated autoimmunity. We found that Nlrp12 plays a protective role in induced EAE by reducing IFNγ/IL-4 ratio in lymph nodes, whereas it potentiates the development of spontaneous EAE (spEAE) in 2D2 T cell receptor (TCR) transgenic mice. Looking into the mechanism of Nlrp12 activity in T cell response, we found that it inhibits T cell proliferation and suppresses Th1 response by reducing IFNγ and IL-2 production. Following TCR activation, Nlrp12 inhibits Akt and NF-κB phosphorylation, while it has no effect on S6 phosphorylation in the mTOR pathway. In conclusion, we propose a model that can explain the dual immunoregulatory function of Nlrp12 in EAE. We also propose a model explaining the molecular mechanism of Nlrp12-dependent regulation of T cell response. View Full-Text
Keywords: Nlrp12; CNS; inflammation; T cell; EAE; spontaneous EAE; TCR signaling; 2D2 Nlrp12; CNS; inflammation; T cell; EAE; spontaneous EAE; TCR signaling; 2D2
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Gharagozloo, M.; Mahmoud, S.; Simard, C.; Mahvelati, T.M.; Amrani, A.; Gris, D. The Dual Immunoregulatory function of Nlrp12 in T Cell-Mediated Immune Response: Lessons from Experimental Autoimmune Encephalomyelitis. Cells 2018, 7, 119.

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