scholarly journals Th17 and regulatory T cells: rebalancing pro- and anti-inflammatory forces in autoimmune arthritis

Rheumatology ◽  
2009 ◽  
Vol 48 (6) ◽  
pp. 602-606 ◽  
Author(s):  
K. Nistala ◽  
L. R. Wedderburn
Author(s):  
Anne M. Pesenacker ◽  
Lucy R. Wedderburn

In recent years, there have been many new developments in the field of regulatory T cells (Treg), challenging the consensus on their behaviour, classification and role(s) in disease. The role Treg might play in autoimmune disease appears to be more complex than previously thought. Here, we discuss the current knowledge of regulatory T cells through animal and human research and illustrate the recent developments in childhood autoimmune arthritis (juvenile idiopathic arthritis (JIA)). Furthermore, this review summarises our understanding of the fields and assesses current and future implications for Treg in the treatment of JIA.


PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e54884 ◽  
Author(s):  
Mattias N. D. Svensson ◽  
Sofia E. M. Andersson ◽  
Malin C. Erlandsson ◽  
Ing-Marie Jonsson ◽  
Anna-Karin H. Ekwall ◽  
...  

2009 ◽  
Vol 61 (8) ◽  
pp. 1043-1050 ◽  
Author(s):  
Sung HoChang ◽  
Eun Jung Jung ◽  
Youn Hee Park ◽  
Dong Gyun Lim ◽  
Na Young Ko ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (1) ◽  
pp. e0117825 ◽  
Author(s):  
Massimo Maddaloni ◽  
Irina Kochetkova ◽  
SangMu Jun ◽  
Gayle Callis ◽  
Theresa Thornburg ◽  
...  

2019 ◽  
Vol 14 (4) ◽  
pp. 508-524 ◽  
Author(s):  
Heike Schmitt ◽  
Julia Ulmschneider ◽  
Ulrike Billmeier ◽  
Michael Vieth ◽  
Patrizio Scarozza ◽  
...  

Abstract Background and Aims The topically applied Toll-like receptor 9 [TLR9] agonist cobitolimod is a first-in-class DNA-based oligonucleotide with demonstrated therapeutic efficacy in clinical trials with ulcerative colitis [UC] patients. We here characterized its anti-inflammatory mechanism in UC. Methods Luminal cobitolimod administration was evaluated in an experimental dextran sodium sulfate [DSS]-induced colitis model. Cultured blood and mucosal cells from UC patients were treated with cobitolimod and analysed via microarray, quantitative real-time PCR, ELISA and flow cytometry. Intestinal slides of cobitolimod-treated UC patients were analysed by immunohistochemistry. Results Cobitolimod administration markedly suppressed experimental colitis activity, and microarray analyses demonstrated mucosal IL10 upregulation and suppression of IL17 signalling pathways. Cobitolimod treatment was associated with significant induction of mucosal IL10+Tr1 and Treg cells and suppression of Th17 cells. TLR9 knockout mice indicated that cobitolimod requires TLR9 signalling for IL10 induction. In UC patients, mucosal TLR9 levels correlated with severity of inflammation. Cobitolimod inhibited IL17A and IL17F, but increased IL10 and FoxP3 expression in cultured intestinal UC T cells. Cobitolimod-mediated suppression of intestinal IL17+T cells was abrogated by IL10 blockade. Furthermore, cobitolimod led to heightened IL10 production by wound healing macrophages. Immunohistochemistry in intestinal biopsies of cobitolimod-treated UC patients indicated increased presence of IL10+mononuclear and regulatory T cells, as well as reduction of IL17+cells. Conclusion Activation of TLR9 via cobitolimod might represent a novel therapeutic approach in UC, as it suppresses Th17 cells and induces anti-inflammatory IL10+macrophages and regulatory T cells, thereby modifying the dysregulated intestinal cytokine balance. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast


2009 ◽  
Vol 61 (8) ◽  
pp. 1043-1050 ◽  
Author(s):  
Sung Ho Chang ◽  
Eun Jung Jung ◽  
Youn Hee Park ◽  
Dong Gyun Lim ◽  
Na Young Ko ◽  
...  

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