Impaired TGF-β signaling in patients with active systemic lupus erythematosus is associated with an overexpression of IL-22
| Autor: | Imen Zamali, Monia Khanfir, Houman Mh, Mohamed-Ridha Barbouche, Skander Mrad, Soumaya Marzouki, Raja Rekik, Asma Beldi-Ferchiou, Melika Ben Ahmed, S. Hamzaoui, T. Larbi, Ons Kammoun |
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| Přispěvatelé: | Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hôpital La Rabta [Tunis], Université de Tunis El Manar (UTM), Centre Hospitalier Universitaire Mongi Slim [La Marsa], Laboratoire d'immunologie clinique [Institut Pasteur de Tunis], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported by the Tunisian Ministry of Higher Education and Research. |
| Rok vydání: | 2018 |
| Předmět: |
Adult
0301 basic medicine Tunisia T-Lymphocytes CD3 Immunology Smad3 pathway Gene Expression Smad2 Protein Biochemistry Immune tolerance Transforming Growth Factor beta1 Pathogenesis Interleukin 22 Young Adult 03 medical and health sciences Systemic lupus erythematosus Immune system TGF-β1 Immune Tolerance IL-22 Humans Lupus Erythematosus Systemic Immunology and Allergy Medicine Phosphorylation skin and connective tissue diseases Molecular Biology Aged Interleukin-15 biology business.industry Interleukins Interleukin Hematology Middle Aged 3. Good health 030104 developmental biology IL-15 Interleukin 15 Cancer research biology.protein Female Signal transduction business [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Signal Transduction |
| Zdroj: | Cytokine Cytokine, Elsevier, 2018, 108, pp.182-189. ⟨10.1016/j.cyto.2018.04.011⟩ |
| ISSN: | 1043-4666 1096-0023 |
| Popis: | International audience; The mechanisms leading to the disruption of self-tolerance in systemic lupus erythematosus (SLE) remain elusive. Herein, we aimed to decipher the molecular basis of the impaired response of mononuclear cells to TGF-β1. The Smad3-pathway was explored on CD3+ lymphocytes in either active or non active SLE patients. An impaired transcription of TGF-β1 target genes was demonstrated in the CD3+ lymphocytes of active SLE patients confirming that the defect involves T cells and pointing to its extrinsic nature. We further demonstrate that the defect did not result from an impaired TGF-βRII expression or Smad2/3 phosphorylation suggesting that the mechanism lies downstream Smad2/3 translocation. Interestingly, the TGF-1 signaling defect did not correlate with an increased expression of soluble or membrane-bound IL-15. However, it was associated with an overexpression of IL-22. This suggests that an excessive activation of AhR pathway (through UV radiations, infections, etc.) could lead to the inhibition of immunosuppressive actions of TGF-β thus disrupting immune homeostasis in SLE. Collectively, our data suggest that the impaired response to TGF-β in SLE patients is associated with disease activity and provide new insights into the pathogenesis of SLE since it could establish the link between the environmental factors and the aberrancies of the immune system usually described in SLE. |
| Databáze: | OpenAIRE |
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