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PMID: 22835828 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology ·Vol. 26 ·No. 11 ·2012-11-00 ·Pages 4722-32

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

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.

MeSH Terms
Adult Aged Autoantibodies Autophagy/physiology Enzyme-Linked Immunosorbent Assay Female Fluorescent Antibody Technique, Indirect Gene Expression Regulation Humans Immunoglobulin G/blood Lupus Erythematosus, Systemic/immunology Male Middle Aged Real-Time Polymerase Chain Reaction T-Lymphocytes/physiology Young Adult
Chemicals
Autoantibodies Immunoglobulin G
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Alessandri Cristiano
Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza University, Rome, Italy.
Barbati Cristiana
Vacirca Davide
Piscopo Paola
Confaloni Annamaria
Sanchez Massimo
Maselli Angela
Colasanti Tania
Conti Fabrizio
Truglia Simona
Perl Andras
Valesini Guido
Malorni Walter
Ortona Elena
Pierdominici Marina
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Article Info
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Abbr.
FASEB J
ISSN
1530-6860
DOI
10.1096/fj.12-206060
Published
2012-11-00
Epub
2012-00-26
Pages
4722-32
Language
English
Region
United States
NLM ID
8804484
PMCID
PMC3475261
Subset
IM
Grants
NIAID NIH HHS · AI048079 · United States
NIAID NIH HHS · AI072648 · United States
NIAID NIH HHS · R56 AI048079 · United States
NIAID NIH HHS · R01 AI048079 · United States
NIAID NIH HHS · R01 AI072648 · United States
External Links
PubMed source DOI: 10.1096/fj.12-206060 PMC Full Text View journal details
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