Cristiano Alessandri,
Cristiana Barbati,
Davide Vacirca,
Paola Piscopo,
Annamaria Confaloni,
Massimo Sanchez,
Angela Maselli,
Tania Colasanti,
Fabrizio Conti,
Simona Truglia, Andras Perl,
Guido Valesini,
Walter Malorni,
Elena Ortona,
Marina Pierdominici
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ABSTRACT: Autophagy, the cytoprotection mechanism that takes place under metabolic impairment, has been implicated in the pathogenesis of autoimmunity. Here, we investigated the spontaneous and induced autophagic behavior of T lymphocytes from patients with systemic lupus erythematosus (SLE) compared with that of T lymphocytes from healthy donors by measuring the autophagy marker microtubule-associated protein 1 light chain 3 (LC3)-II. No significant differences in spontaneous autophagy were found between T lymphocytes from patients with SLE and from healthy donors, apart from CD4(+) naive T cells from patients with SLE in which constitutively higher levels of autophagy (P<0.001) were detected. At variance, whereas treatment of T lymphocytes from healthy donors with serum IgG from patients with SLE resulted in a 2-fold increase in LC3-II levels (P<0.001), T lymphocytes from SLE patients were resistant to autophagic induction and also displayed an up-regulation of genes negatively regulating autophagy, e.g., α-synuclein. These findings could open new perspectives in the search for pathogenetic determinants of SLE progression and in the development of therapeutic strategies aimed to recover T-cell compartment homeostasis by restoring autophagic susceptibility.-Alessandri, C., Barbati, C., Vacirca, D., Piscopo, P., Confaloni, A., Sanchez, M., Maselli, A., Colasanti, T., Conti, F., Truglia, S., Perl, A., Valesini, G., Malorni, W., Ortona, E., Pierdominici, M. T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy.
The FASEB Journal 07/2012; · 5.71 Impact Factor
