Resistance to Exogenous TGF-β Effects in Patients with Systemic Lupus Erythematosus.
2011
Elbeldi-Ferchiou, Asma | Ben Ahmed, Mélika | Smiti-Khanfir, Monia | Houman, Mohamed Habib | Abdeladhim, Maha | Belhadj Hmida, Nadia | Cerf-Bensussan, Nadine | Louzir, Hechmi | Institut Pasteur de Tunis ; Pasteur Network (Réseau International des Instituts Pasteur) | Tunis El Manar University [University of Tunis El Manar] [Tunisia] = Université de Tunis El Manar [Tunisie] = جامعة تونس المنار (ar) (UTM) | Department of Internal Medicine ; La Rabda Hospital | Interactions de l'épithelium intestinal et du système immunitaire (UMR_S 793) ; Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
International audience
Afficher plus [+] Moins [-]anglais. BACKGROUND: The mechanisms underlying the loss of self-tolerance in systemic lupus erythematosus (SLE) are incompletely deciphered. TGF-β plays a key role in self-tolerance demonstrated by the onset of a fatal autoimmune syndrome associated with lupus autoantibodies in mice lacking a functional TGF-β receptor. The present work aims to define whether resistance to TGF-β might contribute to the pathogenesis of SLE. METHODS: Twenty-two patients with active SLE, 16 with other connective tissue diseases, and 10 healthy controls were prospectively included in this study. The effects of exogenous TGF-β1 on IL-2-dependent T-cell proliferation, IFN-γ secretion, and target gene transcription were analyzed on peripheral blood mononuclear cells. RESULTS: Our results showed that 75% of patients with SLE or other connective tissue diseases were totally or partially resistant to the effects of TGF-β1. The responses to the anti-proliferative and transcriptional effects of TGF-β were, however, discordant in a high proportion of our patients. Hence, we distinguish three distinct profiles of resistance to TGF-β1 and suggest that patients may exhibit different defects affecting distinct points of TGF-β1 signaling pathways. CONCLUSION: Our data demonstrate the presence of an impaired response of peripheral cells to TGF-β1 in patients with active SLE that may participate to the pathogenesis of the disease. Further studies will be necessary to delineate the mechanisms underlying the lymphocyte resistance to TGF-β1 in SLE.
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