Polymerization of misfolded Z alpha-1antitrypin protein lowers CX3CR1 expression in human PBMCs

Srinu Tumpara, Matthias Ballmaier, Sabine Wrenger, Mandy König, Matthias Lehmann, Ralf Lichtinghagen, Beatriz Martinez-Delgado, Elena Korenbaum, David DeLuca, Nils Jedicke, Tobias Welte, Malin Fromme (+3 others)
2021 eLife  
The CX3CR1 (chemokine (C-X3-C motif) receptor 1) expression levels on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. The factors implicated in the regulation of CX3CR1 and its specific ligand CX3CL1 (fractalkine) expression remain largely unknown. Recent studies provide evidence that host's misfolded proteins occurring in the forms of polymers or amyloid fibrils can regulate CX3CR1 expression. Herein, a novel example
more » ... monstrates that polymers of human ZZ alpha-1 antitrypsin (Z-AAT) protein, resulting from its conformational misfolding due to the Z (Glu342Lys) mutation in SERPINA1 gene, strongly lower CX3CR1 mRNA expression in human PBMCs. This parallels with increase of intracellular levels of CX3CR1 and Z-AAT proteins. Presented data indicate the involvement of the CX3CR1 pathway in the Z-AAT-related disorders and further support the role of misfolded proteins in CX3CR1 regulation.
doi:10.7554/elife.64881 fatcat:3ak4w5cslfha5fujjix6gpbwte