T lymphocytes from patients with Systemic Lupus Erythematosus (SLE) display multiple abnormalities, including increased cell activation, abnormal cell death by apoptosis and impairment of autophagy pathway. In the present study we report the presence of specific antibodies to D4GDI, a small GTPase family inhibitor, in a significant percentage (46%) of SLE patient sera. We also found a significant association between the presence of these autoantibodies and hematologic manifestations occurring in these patients. Investigating the possible implication of anti-D4GDI autoantibodies in SLE pathogenesis or progression, we found that these antibodies were capable of binding D4GDI expressed at the lymphocyte surface and triggering a series of subcellular events, including Rho GTPase activation. These antibodies were also able to induce autophagy in T cells from both healthy donors and SLE patients, but only those negative to these antibodies. We can conclude that anti-D4GDI autoantibodies could be capable of triggering important responses in T cells such as cytoskeleton remodeling and autophagy pathway and that, in SLE patients, the chronic exposure to these specific autoantibodies could lead to the selection of autophagy-resistant T cell clones contributing to the pathogenesis of the disease.

Autoantibodies specific to D4GDI modulate Rho GTPase mediated cytoskeleton remodeling and induce autophagy in T lymphocytes / Barbati, Cristiana; Alessandri, Cristiano; Vomero, Marta; Vona, R; Colasanti, Tania; Vacirca, D; Camerini, S; Crescenzi, M; Pendolino, Monica; Truglia, Simona; Conti, Fabrizio; Garofalo, Tina; Sorice, Maurizio; Pierdominici, M; Valesini, Guido; Malorni, W; Ortona, E.. - In: JOURNAL OF AUTOIMMUNITY. - ISSN 0896-8411. - STAMPA. - 58:(2015), pp. 78-89. [10.1016/j.jaut.2015.01.005]

Autoantibodies specific to D4GDI modulate Rho GTPase mediated cytoskeleton remodeling and induce autophagy in T lymphocytes.

BARBATI, CRISTIANA;ALESSANDRI, cristiano;VOMERO, MARTA;COLASANTI, TANIA;PENDOLINO, MONICA;TRUGLIA, SIMONA;CONTI, FABRIZIO;GAROFALO, TINA;SORICE, Maurizio;VALESINI, Guido;
2015

Abstract

T lymphocytes from patients with Systemic Lupus Erythematosus (SLE) display multiple abnormalities, including increased cell activation, abnormal cell death by apoptosis and impairment of autophagy pathway. In the present study we report the presence of specific antibodies to D4GDI, a small GTPase family inhibitor, in a significant percentage (46%) of SLE patient sera. We also found a significant association between the presence of these autoantibodies and hematologic manifestations occurring in these patients. Investigating the possible implication of anti-D4GDI autoantibodies in SLE pathogenesis or progression, we found that these antibodies were capable of binding D4GDI expressed at the lymphocyte surface and triggering a series of subcellular events, including Rho GTPase activation. These antibodies were also able to induce autophagy in T cells from both healthy donors and SLE patients, but only those negative to these antibodies. We can conclude that anti-D4GDI autoantibodies could be capable of triggering important responses in T cells such as cytoskeleton remodeling and autophagy pathway and that, in SLE patients, the chronic exposure to these specific autoantibodies could lead to the selection of autophagy-resistant T cell clones contributing to the pathogenesis of the disease.
2015
autophagy; cytoskeleton; D4GDI; Lipid rafts; Systemic lupus erythematosus
01 Pubblicazione su rivista::01a Articolo in rivista
Autoantibodies specific to D4GDI modulate Rho GTPase mediated cytoskeleton remodeling and induce autophagy in T lymphocytes / Barbati, Cristiana; Alessandri, Cristiano; Vomero, Marta; Vona, R; Colasanti, Tania; Vacirca, D; Camerini, S; Crescenzi, M; Pendolino, Monica; Truglia, Simona; Conti, Fabrizio; Garofalo, Tina; Sorice, Maurizio; Pierdominici, M; Valesini, Guido; Malorni, W; Ortona, E.. - In: JOURNAL OF AUTOIMMUNITY. - ISSN 0896-8411. - STAMPA. - 58:(2015), pp. 78-89. [10.1016/j.jaut.2015.01.005]
File allegati a questo prodotto
File Dimensione Formato  
Barbati_Autoantibodies_2015.pdf

solo gestori archivio

Tipologia: Documento in Post-print (versione successiva alla peer review e accettata per la pubblicazione)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 2.09 MB
Formato Adobe PDF
2.09 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/760425
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 14
social impact