Immunopathogenesis of Rheumatoid Arthritis

Slides:



Advertisements
Similar presentations
Cytokines: Introduction
Advertisements

Rheumatoid arthritis The Lancet
Volume 42, Issue 2, Pages (February 2015)
Volume 47, Issue 3, Pages (September 2017)
Volume 17, Issue 6, Pages (June 2013)
CD5: A New Partner for IL-6
Bridget A. Robinson, Timothy J. Nice  Immunity 
Bugs and Brain: How Infection Makes You Feel Blue
The Leptin Connection: Regulatory T Cells and Autoimmunity
Alan N. Houghton, Hiroshi Uchi, Jedd D. Wolchok  Cancer Cell 
Nat. Rev. Rheumatol. doi: /nrrheum
Stop Press: Eosinophils Drafted to Join the Th17 Team
Atopic dermatitis results in intrinsic barrier and immune abnormalities: Implications for contact dermatitis  Julia K. Gittler, BA, James G. Krueger,
The Birds, the Bees, and Innate Immunity
Koen Schepers, Timothy B. Campbell, Emmanuelle Passegué  Cell Stem Cell 
Steven G. Deeks, Russell Tracy, Daniel C. Douek  Immunity 
The Cardiovascular Biology of Glucagon-like Peptide-1
Arturo Casadevall, Liise-anne Pirofski  Cell Host & Microbe 
Aging-related inflammation in osteoarthritis
GM-CSF: From Growth Factor to Central Mediator of Tissue Inflammation
The Multitasking Organ: Recent Insights into Skin Immune Function
Widespread Immunological Functions of Mast Cells: Fact or Fiction?
John J. O'Shea, Robert Plenge  Immunity 
Arming Treg Cells at the Inflammatory Site
Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation
Lung Homeostasis: Influence of Age, Microbes, and the Immune System
The Multitasking Organ: Recent Insights into Skin Immune Function
Roles for KRAS in Pancreatic Tumor Development and Progression
Dietmar M.W. Zaiss, William C. Gause, Lisa C. Osborne, David Artis 
Figure 1 The current model of the pathogenesis of SLE
Arturo Casadevall, Liise-anne Pirofski  Cell Host & Microbe 
John T. Chang, William J. Sandborn  Gastroenterology 
The Role of Retinoic Acid in Tolerance and Immunity
Figure 2 GM-CSF — a key player in inflammation and autoimmunity
Phagocytosis Immunity Volume 22, Issue 5, Pages (May 2005)
Chengcheng Jin, Jorge Henao-Mejia, Richard A. Flavell  Cell Metabolism 
Microbes, Microbiota, and Colon Cancer
Immunology of Food Allergy
F. Berenbaum  Osteoarthritis and Cartilage 
Inflammation in joint injury and post-traumatic osteoarthritis
Tumor Promotion via Injury- and Death-Induced Inflammation
Mechanisms of Contact Sensitization Offer Insights into the Role of Barrier Defects vs. Intrinsic Immune Abnormalities as Drivers of Atopic Dermatitis 
Translating Inflammatory Bowel Disease Research into Clinical Medicine
Volume 393, Issue 10174, Pages (March 2019)
Sarah L. Lebeis, Daniel Kalman  Cell Host & Microbe 
From Vanilla to 28 Flavors: Multiple Varieties of T Regulatory Cells
Subhra K. Biswas, Raffaella Bonecchi  Cell Metabolism 
Monocyte-Macrophages and T Cells in Atherosclerosis
Tobias R. Kollmann, Ofer Levy, Ruth R. Montgomery, Stanislas Goriely 
A New “Immunological” Role for Adipocytes in Obesity
Inflammation, ROS, and Mutagenesis
Asthma and Allergic Inflammation
The Cardiovascular Biology of Glucagon-like Peptide-1
GM-CSF: From Growth Factor to Central Mediator of Tissue Inflammation
Figure 4 Role of chemokines in dendritic cell migration
Cytokine Signaling Modules in Inflammatory Responses
Eystein S. Husebye, Mark S. Anderson  Immunity 
Eystein S. Husebye, Mark S. Anderson  Immunity 
Regulatory T Cells in Asthma
Inflammation 2010: New Adventures of an Old Flame
Volume 75, Issue 7, Pages (April 2009)
Cross-regulation of Signaling Pathways by Interferon-γ: Implications for Immune Responses and Autoimmune Diseases  Xiaoyu Hu, Lionel B. Ivashkiv  Immunity 
Steven G. Deeks, Russell Tracy, Daniel C. Douek  Immunity 
Nathalie Ganne-Carrié, Pierre Nahon  Journal of Hepatology 
Macrophages, Immunity, and Metabolic Disease
Regulatory T Cells and Inflammation: Better Late Than Never
Even Neurons Are Excited by Th17 Cells
Dietmar M.W. Zaiss, William C. Gause, Lisa C. Osborne, David Artis 
Marking Emerging β- and γδ-Selected T Cells
γδ T Cells and the Lymphoid Stress-Surveillance Response
Presentation transcript:

Immunopathogenesis of Rheumatoid Arthritis Gary S. Firestein, Iain B. McInnes  Immunity  Volume 46, Issue 2, Pages 183-196 (February 2017) DOI: 10.1016/j.immuni.2017.02.006 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Sequence of Events Leading to the Development of Clinically Detectable Rheumatoid Arthritis: Two Potential Models In model A (left), a pre-RA phase comprises early generation of autoantibodies (ACPAs) that can bind post-translationally modified self-proteins, particularly via citrullination. This is followed by amplification of the range of specificities of ACPA and by the elaboration of cytokines and chemokines, complement, and metabolic disturbance in the months prior to clinical development of disease. A transition event that requires a “second hit” (as yet poorly understood) permits the development of synovitis. The latter is characterized by frank inflammation, stromal compartment changes, and tissue modification leading to articular damage. In model B (right), which is not mutually exclusive, there is an early interaction between innate immune activation and stromal factors that lead to stromal cell alteration, including epigenetic modifications that initiate a cycle of inflammatory stromal-mediated damage. Autoimmunity can arise as a result of these interactions that in turn can contribute directly or in an amplification loop to disease perpetuation. Immunity 2017 46, 183-196DOI: (10.1016/j.immuni.2017.02.006) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 2 Myeloid Cells, Particularly Macrophages, Are Central to the Perpetuation of Disease Pathogenesis Pathways that can activate macrophages in RA synovitis are shown that promote cytokine release—IL-6 and TNF in particular, and probably GM-CSF, are of central importance as defined by the clear therapeutic benefits achieved upon their inhibition. Immunity 2017 46, 183-196DOI: (10.1016/j.immuni.2017.02.006) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 3 Mechanisms that Drive the Chronicity of RA Distinct pathways combine to mediate failed resolution of disease—these include adaptive, innate, and stromal components with additional impact of the systemic features of disease. The latter may be both consequence of the chronic inflammation and could promote the chronicity, e.g., via creation of pro-inflammatory lipid profiles, promotion of bone remodeling, and secondary osteoarthritis. Immunity 2017 46, 183-196DOI: (10.1016/j.immuni.2017.02.006) Copyright © 2017 Elsevier Inc. Terms and Conditions