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Sertoli cells have a functional NALP3 inflammasome that can modulate autophagy and cytokine production

Hayrabedyan, S and Todorova, K and Jabeen, A and Metodieva, G and Toshkov, S and Metodiev, M and Mincheff, M and Fern�ndez, N (2016) 'Sertoli cells have a functional NALP3 inflammasome that can modulate autophagy and cytokine production.' Scientific Reports, 6 (18896). 18896-. ISSN 2045-2322

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Sertoli cells, can function as non-professional tolerogenic antigen-presenting cells, and sustain the blood-testis barrier formed by their tight junctions. The NOD-like receptor family members and the NALP3 inflammasome play a key role in pro-inflammatory innate immunity signalling pathways. Limited data exist on NOD1 and NOD2 expression in human and mouse Sertoli cells. Currently, there is no data on inflammasome expression or function in Sertoli cells. We found that in primary pre-pubertal Sertoli cells and in adult Sertoli line, TLR4\NOD1 and NOD2 crosstalk converged in NF?B activation and elicited a NALP3 activation, leading to de novo synthesis and inflammasome priming. This led to caspase-1 activation and IL-1? secretion. We demonstrated this process was controlled by mechanisms linked to autophagy. NOD1 promoted pro-IL-1? restriction and autophagosome maturation arrest, while NOD2 promoted caspase-1 activation, IL-1? secretion and autophagy maturation. NALP3 modulated NOD1 and pro-IL-1? expression, while NOD2 inversely promoted IL-1?. This study is proof of concept that Sertoli cells, upon specific stimulation, could participate in male infertility pathogenesis via inflammatory cytokine induction.

Item Type: Article
Uncontrolled Keywords: Blood-Testis Barrier; Sertoli Cells; Antigen-Presenting Cells; Tight Junctions; Animals; Mice, Inbred BALB C; Mice; Caspase 1; NF-kappa B; Signal Transduction; Gene Expression Regulation; Autophagy; Male; Toll-Like Receptor 4; Interleukin-1beta; Nod2 Signaling Adaptor Protein; Nod1 Signaling Adaptor Protein; Immunity, Innate; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 11 Feb 2016 12:12
Last Modified: 15 Jan 2022 00:23

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