The Th17 family: flexibility follows function.
Reads0
Chats0
TLDR
The developmental and functional features of Th17 cells in relation to iTreg cells, Th1 cells, and Th22 cells are examined, as a basis for understanding the contributions of this pathway to host defense, immune homeostasis, and immune‐mediated disease.Abstract:
Discovery of the T-helper 17 (Th17) subset heralded a major shift in T-cell biology and immune regulation. In addition to defining a new arm of the adaptive immune response, studies of the Th17 pathway have led to a greater appreciation of the developmental flexibility, or plasticity, that is a feature of T-cell developmental programs. Since the initial finding that differentiation of Th17 cells is promoted by transforming growth factor-β (TGFβ), it became clear that Th17 cell development overlapped that of induced regulatory T (iTreg) cells. Subsequent findings established that Th17 cells are also unusually flexible in their late developmental programming, demonstrating substantial overlap with conventional Th1 cells through mechanisms that are just beginning to be understood but would appear to have important implications for immunoregulation at homeostasis and in immune-mediated diseases. Herein we examine the developmental and functional features of Th17 cells in relation to iTreg cells, Th1 cells, and Th22 cells, as a basis for understanding the contributions of this pathway to host defense, immune homeostasis, and immune-mediated disease.read more
Citations
More filters
Journal ArticleDOI
T cell subsets and their signature cytokines in autoimmune and inflammatory diseases
TL;DR: Whether Th cell pathogenicity can be defined solely based on their cytokine profiles and whether rigid definition of a Th cell subset by its cytokine profile is helpful are discussed.
Journal ArticleDOI
Sex steroid deficiency–associated bone loss is microbiota dependent and prevented by probiotics
Jau-Yi Li,Benoit Chassaing,Abdul Malik Tyagi,Chiara Vaccaro,Tao Luo,Jonathan Adams,Trevor Darby,M. Neale Weitzmann,Jennifer G. Mulle,Andrew T. Gewirtz,Rheinallt M. Jones,Roberto Pacifici +11 more
TL;DR: It is demonstrated that twice-weekly treatment of sex steroid-deficient mice with the probiotics Lactobacillus rhamnosus GG (LGG) or the commercially available probiotic supplement VSL#3 reduces gut permeability, dampens intestinal and BM inflammation, and completely protects against bone loss, suggesting that probiotics that decrease Gut permeability have potential as a therapeutic strategy for postmenopausal osteoporosis.
Journal ArticleDOI
MicroRNA-mediated regulation of T helper cell differentiation and plasticity
Dirk Baumjohann,K. Mark Ansel +1 more
TL;DR: Recent advances and emerging ideas about how microRNAs — small endogenously expressed oligonucleotides that modulate gene expression — are involved in the regulatory networks that determine TH cell fate decisions and that regulate their effector functions are discussed.
Journal ArticleDOI
The Role of IL-17 and Related Cytokines in Inflammatory Autoimmune Diseases.
TL;DR: The roles of cytokines that promote the development and maintenance of pathogenic Th17 cells in autoimmune diseases are highlighted, which strongly contributes to autoimmune diseases that are accompanied by chronic inflammation.
Journal ArticleDOI
Control of lupus nephritis by changes of gut microbiota
Qinghui Mu,Husen Zhang,Xiaofeng Liao,Kaisen Lin,Hualan Liu,Hualan Liu,Michael R. Edwards,S. Ansar Ahmed,Ruoxi Yuan,Ruoxi Yuan,Liwu Li,Thomas E. Cecere,David B. Branson,Jay L. Kirby,Poorna Goswami,Caroline M. Leeth,Kaitlin A. Read,Kenneth J. Oestreich,Miranda D. Vieson,Christopher M. Reilly,Christopher M. Reilly,Xin M. Luo +21 more
TL;DR: These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner, and demonstrates essential mechanisms on how changes of the Gut microbiota regulate l upus-associated immune responses in mice.
References
More filters
Journal ArticleDOI
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells.
Estelle Bettelli,Yijun Carrier,Wenda Gao,Thomas Korn,Terry B. Strom,Mohamed Oukka,Howard L. Weiner,Vijay K. Kuchroo +7 more
TL;DR: It is shown that IL-6, an acute phase protein induced during inflammation, completely inhibits the generation of Foxp3+ Treg cells induced by TGF-β, and the data demonstrate a dichotomy in thegeneration of pathogenic (TH17) T cells that induce autoimmunity and regulatory (Foxp3+) T Cells that inhibit autoimmune tissue injury.
Journal ArticleDOI
The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.
Ivaylo I. Ivanov,Brent S. McKenzie,Liang Zhou,Carlos E. Tadokoro,Alice Lepelley,Juan J. Lafaille,Daniel J. Cua,Dan R. Littman +7 more
TL;DR: It is shown that the orphan nuclear receptor RORgammat is the key transcription factor that orchestrates the differentiation of this effector cell lineage of proinflammatory T helper cells and its potential as a therapeutic target in inflammatory diseases is highlighted.
Journal ArticleDOI
Interleukin 17–producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
Laurie E. Harrington,Robin D. Hatton,Paul R. Mangan,Henrietta Turner,Theresa L. Murphy,Kenneth M. Murphy,Casey T. Weaver +6 more
TL;DR: Findings provide a basis for understanding how inhibition of IFN-γ signaling enhances development of pathogenic TH-17 effector cells that can exacerbate autoimmunity.
Journal ArticleDOI
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Heon Park,Zhaoxia Li,Xuexian O. Yang,Seon Hee Chang,Roza Nurieva,Yi Hong Wang,Ying Wang,Leroy Hood,Zhou Zhu,Qiang Tian,Chen Dong +10 more
TL;DR: In vivo, antibody to IL- 17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused Chemokine production and leukocyte infiltration, indicating a unique T helper lineage that regulates tissue inflammation.
Journal ArticleDOI
TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-Producing T cells
Marc Veldhoen,Richard J. Hocking,Christopher J. Atkins,Richard M. Locksley,Brigitta Stockinger +4 more
TL;DR: The data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation ofIL-17-producing T cells.