TNF-blocking therapy is successfully used in the treatment of immune-mediated and inflammatory diseases. Although the inhibition of inflammatory pathways in target tissues by anti-TNF therapy has been clearly described, the impact of TNF-blockade on peripheral T cell responses in humans is still unclear. Here we studied T cell effector functions in psoriasis patients before and after treatment with anti-TNF by measuring a wide panel of cytokines as well as cell division upon in vitro stimulation. In parallel, the modulation of T cell cytokine gene expression was evaluated in psoriatic skin lesions. Results clearly evidenced that TNF-blockade increases T cell cytokine responses, mainly Th1 and Th17, in peripheral lymphocytes upon stimulation. Importantly, TNF-blockade also induced a potent enhancement of IL-10 expression by different subsets of circulating leukocytes that was found to correlate with the clinical outcome of the therapy. Despite the enhanced T cell cytokine responses in the peripheral circulation, in psoriatic skin lesions the overall effect of TNF-blockade was a diminished expression of Th1 and Th17 cytokine genes, paralleled by augmented expression of Il10. These evidences indicate a negative regulatory role of TNF on T cell activation and effector functions and enlighten a new role for TNF-blockade in the up-regulation of IL-10 that may participate to the shut down of the inflammatory reaction. Ongoing work (1): TNF-blockade enhances T cell response to TcR stimulation. Ongoing work (2): Modulation of cytokine gene expression by TNF-therapy in intestinal mucosa of patients with Inflammatory Bowel Disease
(2009). Effect of anti-TNF therapy on T cell activation and effector functions in patients with chronic inflammatory diseases. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2009).
Autori: | ||
Data di pubblicazione: | 26-nov-2009 | |
Tutor esterno: | REALI, EVA | |
Titolo: | Effect of anti-TNF therapy on T cell activation and effector functions in patients with chronic inflammatory diseases | |
Settore Scientifico Disciplinare: | MED/04 - PATOLOGIA GENERALE | |
Lingua: | English | |
Scuola di dottorato: | Scuola di Dottorato in Medicina Traslazionale e Molecolare | |
Corso di dottorato: | MEDICINA TRASLAZIONALE E MOLECOLARE (DIMET) - 45R | |
Ciclo: | 22 | |
Anno Accademico: | 2008/2009 | |
Citazione: | (2009). Effect of anti-TNF therapy on T cell activation and effector functions in patients with chronic inflammatory diseases. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2009). | |
Parole Chiave: | anti-TNF; T-cell; cytokines; immune system; inflammatory diseases | |
Appare nelle tipologie: | 07 - Tesi di dottorato Bicocca post 2009 |
File in questo prodotto:
File | Descrizione | Tipologia | Licenza | |
---|---|---|---|---|
phd_unimib_708362.pdf | Doctoral thesis | Open Access Visualizza/Apri |