Journal ArticleDOI
Type II monocytes modulate T cell-mediated central nervous system autoimmune disease
Martin S. Weber,Thomas Prod'homme,Sawsan Youssef,Shannon E. Dunn,Cynthia D Rundle,Linda Lee,Juan C. Patarroyo,Olaf Stüve,Raymond A. Sobel,Lawrence Steinman,Scott S. Zamvil +10 more
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TLDR
Adoptive transfer of type II monocytes reversed EAE, suppressed TH17 cell development and promoted both TH2 differentiation and expansion of Treg cells in recipient mice, identifying a central role for these cells in T cell immune modulation of autoimmunity.Abstract:
Treatment with glatiramer acetate (GA, copolymer-1, Copaxone), a drug approved for multiple sclerosis (MS), in a mouse model promoted development of anti-inflammatory type II monocytes, characterized by increased secretion of interleukin (IL)-10 and transforming growth factor (TGF)-beta, and decreased production of IL-12 and tumor necrosis factor (TNF). This anti-inflammatory cytokine shift was associated with reduced STAT-1 signaling. Type II monocytes directed differentiation of T(H)2 cells and CD4+CD25+FoxP3+ regulatory T cells (T(reg)) independent of antigen specificity. Type II monocyte-induced regulatory T cells specific for a foreign antigen ameliorated experimental autoimmune encephalomyelitis (EAE), indicating that neither GA specificity nor recognition of self-antigen was required for their therapeutic effect. Adoptive transfer of type II monocytes reversed EAE, suppressed T(H)17 cell development and promoted both T(H)2 differentiation and expansion of T(reg) cells in recipient mice. This demonstration of adoptive immunotherapy by type II monocytes identifies a central role for these cells in T cell immune modulation of autoimmunity.read more
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M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Veronique E. Miron,Amanda Boyd,Jing-Wei Zhao,Tracy J. Yuen,Tracy J. Yuen,Julia M. Ruckh,Jennifer L. Shadrach,Peter van Wijngaarden,Amy J. Wagers,Anna Williams,Robin J.M. Franklin,Charles ffrench-Constant +11 more
TL;DR: It is found that a switch from an M1- to an M2-dominant response occurred in microglia and peripherally derived macrophages as remyelination started and activin-A is identified as a therapeutic target for CNS regeneration.
Journal ArticleDOI
Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice.
Ravid Shechter,Anat London,Chen Varol,Catarina Raposo,Melania Cusimano,Gili Yovel,Asya Rolls,Matthias Mack,Stefano Pluchino,Gianvito Martino,Steffen Jung,Michal Schwartz +11 more
TL;DR: Using a mouse model of spinal injury, Michal Schwartz and colleagues tested the effect of macrophages on the recovery process and demonstrate an important anti-inflammatory role for a subset of infiltrating monocyte-derived macrophage that is dependent upon their expression of interleukin 10.
Journal ArticleDOI
Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions
Ayumi Yoshizaki,Tomomitsu Miyagaki,David J. DiLillo,Takashi Matsushita,Mayuka Horikawa,Evgueni I. Kountikov,Rosanne Spolski,Jonathan C. Poe,Warren J. Leonard,Thomas F. Tedder +9 more
TL;DR: It is shown that B10-cell maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T cells, and that the ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.
Journal ArticleDOI
Multiple Sclerosis: Mechanisms and Immunotherapy
TL;DR: Major challenges for MS research involve understanding the mechanisms of disease progression, developing treatment for progressive MS, and determining the degree to which progressive disease can be prevented by early treatment.
Journal ArticleDOI
Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing.
Qunzhou Zhang,Wenru Su,Shihong Shi,Petra Wilder-Smith,Andy Peng Xiang,Alexander Wong,Andrew L. Nguyen,Chan Wook Kwon,Anh D. Le +8 more
TL;DR: These findings provide first evidence that GMSCs are capable to elicit M2 polarization of macrophages, which might contribute to a marked acceleration of wound healing.
References
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Journal ArticleDOI
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
TL;DR: Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells and retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+.
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
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
RAG-1-deficient mice have no mature B and T lymphocytes
Peter Mombaerts,John Iacomini,Randall S. Johnson,Karl Herrup,Susumu Tonegawa,Virginia E. Papaioannou +5 more
TL;DR: The introduction of a mutation in RAG-1 into the germline of mice via gene targeting in embryonic stem cells is described and it is shown that this mutation either activates or catalyzes the V(D)J recombination reaction of immunoglobulin and T cell receptor genes.
Journal ArticleDOI
Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse.
Mary E. Brunkow,Jeffery Ew,Hjerrild Ka,Bryan W. Paeper,L B Clark,Yasayko Sa,John E. Wilkinson,David J. Galas,Steven F. Ziegler,Fred Ramsdell +9 more
TL;DR: Genetic complementation demonstrates that the protein product of Foxp3, scurfin, is essential for normal immune homeostasis.