Review Th17 and regulatory T lymphocytes in primary biliary cirrhosis and systemic sclerosis as models of autoimmune fibrotic diseases Daniela Fenoglio a, b , Francesca Bernuzzi c , Florinda Battaglia a , Alessia Parodi a , Francesca Kalli a , Simone Negrini a , Raffaele De Palma d , Pietro Invernizzi c, 1 , Gilberto Filaci a, b, ⁎ , 1 a Centre of Excellence for Biomedical Research (CEBR), University of Genoa b Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy c Center for Autoimmune Liver Diseases, IRCCS Istituto Clinico Humanitas, Rozzano, Italy d Department of Clinical and Experimental Medicine, Second University of Naples, c/o II Policlinico abstract article info Article history: Received 2 May 2012 Accepted 12 May 2012 Available online 23 May 2012 Keywords: Primary biliary cirrhosis Systemic Sclerosis Th17 Treg Fibrotic autoimmune diseases are characterized by an inflammatory process in which fibrogenic cytokines, such as TGFβ and IL6, have a major role. Interestingly, these cytokines are also involved in the generation and function of both an effector T lymphocyte subpopulation, the Th17 cells, and the regulatory T lympho- cytes (Treg). These evidences raised the hypothesis that an unbalanced equilibrium induced by the over- production of the fibrogenic cytokines may have pathogenic relevance in fibrotic autoimmune diseases. On this basis, this review analyzes the available data concerning Th17 and Treg generation and function in two representative fibrotic autoimmune diseases, primary biliary cirrhosis (PBC) and systemic sclerosis (SSc), as models for organ-specific and systemic diseases, respectively. With regard to the Th17 cells, their expansion was found to be a common feature associated with a relative contraction of Th1 immune responses. Concerning to the regulatory T cell compartment, quantitative and qualitative alterations were observed in both diseases. However, while PBC patients showed defects only in the CD8 + Treg subset, SSc patients demonstrated abnormalities regarding to both the CD4 + CD25 + and the CD8+ Treg subpopulations. Hence, the CD8+ Treg subset seems to be the most involved in the patho- genic cascade leading to fibrotic disease onset and maintenance. Collectively, the reviewed data support the concept that altered homeostasis between effector and regulatory T cell circuits is present in fibrotic autoimmune diseases and that the major factors responsible for such dis- equilibrium are Th17 cells in the effector arm and CD8 + Treg in the regulatory arm. © 2012 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300 2. Th17 and Treg cells in PBC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301 3. Th17 and Treg cells in SSc . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303 Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Introduction Fibrotic autoimmune diseases are characterized pathogenetically by an inflammatory process which induces and sustains robust fibro- sis. This is due to the production of an array of biological factors acti- vating fibroblast proliferation and collagen secretion. Among the Autoimmunity Reviews 12 (2012) 300–304 ⁎ Corresponding author at: Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV n. 7, 16132, Genova, Italy. Tel.: +39 010 3538984; fax: + 39 010 3533025. E-mail address: gfilaci@unige.it (G. Filaci). 1 Dr. Pietro Invernizzi and Dr. Gilberto Filaci contributed equally to the manuscript. 303 1568-9972/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2012.05.004 Contents lists available at SciVerse ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev