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Open AccessJournal ArticleDOI

Fibrotic disease and the T H 1/T H 2 paradigm

Thomas A. Wynn
- 01 Aug 2004 - 
- Vol. 4, Iss: 8, pp 583-594
TLDR
In this article, the immunological mechanisms that initiate, sustain and suppress the fibrotic process were studied. But the mechanisms that are involved in fibrogenesis are now known to be distinct from those involved in inflammation.
Abstract
Tissue fibrosis (scarring) is a leading cause of morbidity and mortality. Current treatments for fibrotic disorders, such as idiopathic pulmonary fibrosis, hepatic fibrosis and systemic sclerosis, target the inflammatory cascade, but they have been widely unsuccessful, largely because the mechanisms that are involved in fibrogenesis are now known to be distinct from those involved in inflammation. Several experimental models have recently been developed to dissect the molecular mechanisms of wound healing and fibrosis. It is hoped that by better understanding the immunological mechanisms that initiate, sustain and suppress the fibrotic process, we will achieve the elusive goal of targeted and effective therapeutics for fibroproliferative diseases.

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Citations
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Journal ArticleDOI

Protective and pathogenic functions of macrophage subsets

TL;DR: The four stages of orderly inflammation mediated by macrophages are discussed: recruitment to tissues; differentiation and activation in situ; conversion to suppressive cells; and restoration of tissue homeostasis.
Journal ArticleDOI

Cellular and molecular mechanisms of fibrosis.

TL;DR: Current understanding of the cellular and molecular mechanisms of fibrogenesis is explored and components of the renin–angiotensin–aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs.
Journal ArticleDOI

Alternative Activation of Macrophages: An Immunologic Functional Perspective

TL;DR: The cellular sources of these cytokines, receptor signaling pathways, and induced markers and gene signatures are reviewed and the concept of macrophage activation in the context of the immune response is revisit.
Journal ArticleDOI

Mechanisms of fibrosis: therapeutic translation for fibrotic disease

TL;DR: How cell-intrinsic changes in important structural cells can perpetuate the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix–producing myofibroblasts is described.
Journal ArticleDOI

Macrophages in Tissue Repair, Regeneration, and Fibrosis

Thomas A. Wynn, +1 more
- 15 Mar 2016 - 
TL;DR: This review discusses the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing,pro-fibrotic, anti- inflammatory, anti -fib rotic, Pro-resolving, and tissue-regenerating phenotypes after injury, and highlights how some of these mechanisms and macrophage activation states could be exploited therapeutically.
References
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Journal ArticleDOI

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TL;DR: Findings that have advanced the understanding of IL-10 and its receptor are highlighted, as well as its in vivo function in health and disease.
Journal ArticleDOI

Alternative activation of macrophages

TL;DR: The evidence in favour of alternative macrophage activation by the TH2-type cytokines interleukin-4 (IL-4) and IL-13 is assessed, and its limits and relevance to a range of immune and inflammatory conditions are defined.
Book

Pathologic basis of disease

TL;DR: The objective is to establish an experimental procedure and show direct AFM progression from EMT to EMT using a simple, straightforward, and reproducible procedure.
Journal ArticleDOI

Functional diversity of helper T lymphocytes.

TL;DR: The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses.
Journal ArticleDOI

Interleukin-13: Central Mediator of Allergic Asthma

TL;DR: In this paper, the type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma.
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