A Pellino-2 variant is associated with constitutive NLRP3 inflammasome activation in a family with ocular pterygium–digital keloid dysplasia

Cristea I.; Abarca H.; Christensen Mellgren A.E.; Trubnykova M.; Mehrasa R.; Peters D.J.M.; Houge G.; Hennekam R.C.M.; Rødahl E.; Bruland O.; Bredrup C. · FEBS Letters (2023) · DOI: 10.1002/1873-3468.14597

Resumen

Ocular pterygium–digital keloid dysplasia (OPDKD) is a rare hereditary disease characterized by corneal ingrowth of vascularized conjunctival tissue early in life. Later, patients develop keloids on fingers and toes but are otherwise healthy. In a recently described family with OPDKD, we report the presence of a de novo c.770C > T, p.(Thr257Ile) variant in PELI2 in the affected individual. PELI2 encodes for the E3 ubiquitin ligase Pellino-2. In transgenic U87MG cells overexpressing Pellino-2 with the p.(Thr257Ile) amino acid substitution, constitutive activation of the NLRP3 inflammasome was observed. However, the Thr257Ile variant did not affect Pellino-2 intracellular localization, its binding to known interaction partners, nor its stability. Our findings indicate that constitutive autoactivation of the NLRP3 inflammasome contributes to the development of PELI2-associated OPDKD.

Instituciones: Universidad Peruana de Ciencias Aplicadas