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01-10-2013 | Commentary Letter

Which type of inflammation can be controlled by Foxp3+ Tregs?

Author: Thomas Korn

Published in: Acta Neuropathologica | Issue 4/2013

Excerpt

Foxp3+ Tregs are a non-redundant dominant means of maintaining peripheral immune tolerance under homeostatic conditions because depletion of Tregs in adult individuals leads to multi-organ autoimmunity within 3 weeks [9]. Yet, the role of Tregs is more controversial under conditions of ongoing inflammation. Immunopathology in organ-specific autoimmunity in the CNS and joints, and chronic inflammation in the gut are much enhanced in the absence of Foxp3+ Tregs suggesting that Tregs can control ongoing autoimmune inflammation [8, 14, 15]. In infectious inflammation, foreign antigen-specific Foxp3+ Tregs also limit immunopathology [1]. However, in infectious diseases, Tregs are operational at the expense of less efficient pathogen eradication or even chronic infection. Here, effector T cell-intrinsic down-modulatory mechanisms like induction of IL-10 in activated effector T cells are instrumental to limiting immunopathology as well [7]. The interplay and relative importance of Treg-mediated and effector T cell intrinsic control of inflammation in infection and autoimmunity are not well understood. …

Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL (2002) CD4+ CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420:502–507PubMedCrossRef

Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238PubMedCrossRef

Chaudhry A, Rudra D, Treuting P, Samstein RM, Liang Y, Kas A, Rudensky AY (2009) CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326:986–991PubMedCrossRef

Chen Z, Barbi J, Bu S, Yang H-Y, Li Z, Gao Y, Jinasena D, Fu J, Lin F, Chen C, Zhang J, Yu N, Li X, Shan Z, Nie J, Gao Z, Tian H, Li Y, Yao Z, Zheng Y, Park BV, Pan Z, Zhang J, Dang E, Li Z, Wang H, Luo W, Li L, Semenza GL, Zheng SG, Loser K, Tsun A, Greene MI, Pardoll DM, Pan F, Li B (2013) The ubiquitin ligase stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor foxp3. Immunity 39:272–285PubMedCrossRef

Dardalhon V, Awasthi A, Kwon H, Galileos G, Gao W, Sobel RA, Mitsdoerffer M, Strom TB, Elyaman W, Ho I-C, Khoury S, Oukka M, Kuchroo VK (2008) IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(−) effector T cells. Nat Immunol 9:1347–1355PubMedCrossRef

Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, Ahlfors H, Wilhelm C, Tolaini M, Menzel U, Garefalaki A, Potocnik AJ, Stockinger B (2011) Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol 12:255–263PubMedCrossRef

Jankovic D, Kullberg MC, Feng CG, Goldszmid RS, Collazo CM, Wilson M, Wynn TA, Kamanaka M, Flavell RA, Sher A (2007) Conventional T-bet(+) Foxp3(−) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J Exp Med 204:273–283PubMedCrossRef

Kelchtermans H, De Klerck B, Mitera T, Van Balen M, Bullens D, Billiau A, Leclercq G, Matthys P (2005) Defective CD4+ CD25+ regulatory T cell functioning in collagen-induced arthritis: an important factor in pathogenesis, counter-regulated by endogenous IFN-gamma. Arthr Res Ther 7:R402–R415CrossRef

Kim JM, Rasmussen JP, Rudensky AY (2007) Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol 8:191–197PubMedCrossRef

10.

Koch MA, Gas Tucker-Heard, Perdue NR, Killebrew JR, Urdahl KB, Campbell DJ (2009) The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat Immunol 10:595–602PubMedCrossRef

11.

Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen TR, Bäckström BT, Sobel RA, Wucherpfennig KW, Strom TB, Oukka M, Kuchroo VK (2007) Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med 13:423–431PubMedCrossRef

12.

Kurschus FC, Croxford AL, Heinen AP, Wörtge S, Ielo D, Waisman A (2010) Genetic proof for the transient nature of the Th17 phenotype. Eur J Immunol 40:3336–3346PubMedCrossRef

13.

Lowther DE, Chong DL, Ascough S, Ettorre A, Ingram RJ, Boyton RJ, Altmann DM (2013) Th1 not Th17 cells drive spontaneous MS-like disease despite a functional regulatory T cell response. Acta Neuropathol. doi:10.1007/s00401-013-1159-9

14.

Mcgeachy MJ, Stephens LA, Anderton SM (2005) Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+ CD25+ regulatory cells within the central nervous system. J Immunol 175:3025–3032PubMed

15.

Powrie F, Leach MW, Mauze S, Caddle LB, Coffman RL (1993) Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. Int Immunol 5:1461–1471PubMedCrossRef

16.

Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, Ye X, Treuting P, Siewe L, Roers A, Henderson WR, Muller W, Rudensky AY (2008) Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28:546–558PubMedCrossRef

17.

Zheng Y, Chaudhry A, Kas A, Deroos P, Kim JM, Chu T–T, Corcoran L, Treuting P, Klein U, Rudensky AY (2009) Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses. Nature 458:351–356PubMedCrossRef

Title: Which type of inflammation can be controlled by Foxp3+ Tregs?
Author: Thomas Korn
Publication date: 01-10-2013
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 4/2013
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-013-1178-6

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