The TRPC6 intronic polymorphism, associated with the risk of neurological disorders in systemic lupus erythematous, influences immune cell function

• Published in: Journal of neuroimmunology Vol. 325; pp. 43 - 53
• Main Authors: Ramirez, Giuseppe A., Coletto, Lavinia A., Bozzolo, Enrica P., Citterio, Lorena, Delli Carpini, Simona, Zagato, Laura, Rovere-Querini, Patrizia, Lanzani, Chiara, Manunta, Paolo, Manfredi, Angelo A., Sciorati, Clara
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-12-2018
• Subjects: Apoptosis; Calcium; Cytokines; Genetics; Neuropsychiatric; Systemic lupus erythematous; TRPC6; KRH; TRPC6; Calcium; Cytokines; TT SLE; Neuropsychiatric; IQR; Ca+; SLE; PBMCs; TT NPSLE; Systemic lupus erythematous; SNP; AICD; Genetics; NPSLE; Apoptosis
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2018.10.010

Patients with systemic lupus erythematosus (SLE) carrying a TT genotype for the rs7925662 single nucleotide polymorphism (SNP) in the transient receptor potential canonical channel 6 (TRPC6) gene are more likely to develop neuropsychiatric manifestations (NPSLE). We functionally characterised the effects of TRPC6 on peripheral blood mononuclear cells from 18 patients with SLE and 8 healthy controls with a known genotype. TRPC6 influenced calcium currents, apoptosis rates and cytokine secretion in a disease- and genotype-dependent manner. Cells from TT patients with NPSLE were more dependent on TRPC6 for the generation of calcium currents.
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•The TRPC6 rs7925662 intronic SNP (TT genotype) associates with a higher incidence of NPSLE.•Ca2+ currents depend on TRPC6, especially in PBMCs of SLE patients.•The rs7925662 TT genotype associates with enhanced TRPC6 calcium influx in PBMCs of NPSLE patients.•PBMCs of TT SLE patients revealed higher sensitivity to activation induced cell death.•TRPC6 controls IL-17 release in cells from SLE patients.