TY - JOUR
T1 - FoxP3+ regulatory T cells suppress early stages of granuloma formation but have little impact on sarcoidosis lesions
AU - Taflin, Cécile
AU - Miyara, Makoto
AU - Nochy, Dominique
AU - Valeyre, Dominique
AU - Naccache, Jean Marc
AU - Altare, Frédéric
AU - Salek-Peyron, Pascale
AU - Badoual, Cécile
AU - Bruneval, Patrick
AU - Haroche, Julien
AU - Mathian, Alexis
AU - Amoura, Zahir
AU - Hill, Gary
AU - Gorochov, Guy
PY - 2009/1/1
Y1 - 2009/1/1
N2 - Sarcoidosis is characterized by a disproportionate Th1 granulomatous immune response in involved organs. It is also associated with both peripheral and intratissular regulatory T cell (Treg) expansion. These cells exhibit powerful antiproliferative activity , yet do not completely inhibit the production of either tumor necrosis factor-α or interferon-γ. The origin of the observed Treg amplification and, more importantly, its impact on the evolution of sarcoidosis remain unresolved issues. Here, we show that CD4 +CD45RA-FoxP3bright Tregs proliferate and accumulate within granulomas. However, circulating and tissue Treg numbers are neither correlated with the dissemination of the disease nor correlated locally with the extent of granulomatous inflammation. Rather, we found a positive correlation between the presence of Tregs in renal granulomas and the degree of interstitial fibrosis (r = 0.46, P = 0.03, n = 20). Furthermore, Treg depletion accelerates in vitro granuloma growth in mononuclear cell cultures of healthy controls, but not in those from patients with active sarcoidosis. The results of this study show that although healthy Tregs suppress the initial steps of granuloma formation, they have no positive influence on sarcoidosis lesions. Our findings argue for a more preventive than curative effect of Tregs on inflammatory processes.
AB - Sarcoidosis is characterized by a disproportionate Th1 granulomatous immune response in involved organs. It is also associated with both peripheral and intratissular regulatory T cell (Treg) expansion. These cells exhibit powerful antiproliferative activity , yet do not completely inhibit the production of either tumor necrosis factor-α or interferon-γ. The origin of the observed Treg amplification and, more importantly, its impact on the evolution of sarcoidosis remain unresolved issues. Here, we show that CD4 +CD45RA-FoxP3bright Tregs proliferate and accumulate within granulomas. However, circulating and tissue Treg numbers are neither correlated with the dissemination of the disease nor correlated locally with the extent of granulomatous inflammation. Rather, we found a positive correlation between the presence of Tregs in renal granulomas and the degree of interstitial fibrosis (r = 0.46, P = 0.03, n = 20). Furthermore, Treg depletion accelerates in vitro granuloma growth in mononuclear cell cultures of healthy controls, but not in those from patients with active sarcoidosis. The results of this study show that although healthy Tregs suppress the initial steps of granuloma formation, they have no positive influence on sarcoidosis lesions. Our findings argue for a more preventive than curative effect of Tregs on inflammatory processes.
UR - http://www.scopus.com/inward/record.url?scp=59649099784&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2009.080580
DO - 10.2353/ajpath.2009.080580
M3 - Article
C2 - 19147826
AN - SCOPUS:59649099784
SN - 0002-9440
VL - 174
SP - 497
EP - 508
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -