Cγ1 Deficiency Exacerbates Collagen-Induced Arthritis
Richard T Strait1, Sherry Thornton1, Fred D Finkelman2
1Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
Arthritis & Rheumatology (Hoboken, N.J.)
|January 28, 2016
Summary
The absence of IgG1 antibodies in mice increased the severity and frequency of collagen-induced arthritis (CIA). This suggests IgG1 plays a protective role, possibly by modulating the production of other IgG isotypes like IgG2a/c.
Area of Science:
- Immunology
- Rheumatology
Background:
- Immunoglobulin G (IgG) antibodies are crucial for pathogen defense through pathogen aggregation and immune system activation.
- IgG1, a major murine IgG isotype, has limited complement activation and aggregation abilities, and binds avidly to inhibitory Fcγ receptors.
- Previous research indicated IgG1 protects against certain renal diseases independent of complement and FcγR.
Purpose of the Study:
- To investigate the protective role of IgG1 in collagen-induced arthritis (CIA), a disorder dependent on complement and Fcγ receptors.
Main Methods:
- Collagen-induced arthritis (CIA) was induced in mice using type II collagen (CII) or anti-CII monoclonal antibodies.
- Arthritis severity was evaluated, and CII-specific IgG levels were measured in wild-type and IgG1-deficient mice.
Main Results:
- Mice lacking IgG1 (IgG1(-/-)) exhibited increased frequency and severity of CIA compared to IgG1(+/+) mice.
- Disease progression was dependent on FcγRIII and C3 in both mouse strains.
- Higher titers of CII-specific IgG2a/c were observed in IgG1(-/-) mice, correlating with CIA incidence and severity.
Conclusions:
- The absence of a functional Cγ1 gene indirectly promotes CIA development.
- This promotion is likely due to increased production of IgG2a/c, a potent activator of complement and stimulatory FcγR.
Related Concept Videos
01:24T Cell Types and Functions
3.2K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.2K
01:11Fibril-associated Collagen
3.5K
Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
3.5K
01:05Type IV Collagen of Basal Lamina
3.3K
Type IV collagen is a 400 nm long, network-forming collagen that acts as a barrier between the epithelial and endothelial cells. Type IV collagen forms the backbone of the basement membrane by scaffolding with laminin, entactin, proteoglycans, and fibronectin. Apart from rendering structural support to the basement membrane, it also helps entail signaling potentials necessary for both pathological and physiological functions.
A type IV collagen molecule has six alpha chains which can...
A type IV collagen molecule has six alpha chains which can...
3.3K
01:23Rheumatic Heart Disease I: Introduction
840
Rheumatic heart disease or RHD is a chronic condition that results from rheumatic fever, causing permanent damage to the heart valves.Etiology and Risk FactorsIt primarily arises from rheumatic fever, an inflammatory disease that can develop after untreated or inadequately treated group A streptococcal (GAS) pharyngitis. Streptococcus spreads through direct contact with oral or respiratory secretions. While the bacteria are the causative agents, factors like malnutrition, overcrowding, poor...
840
01:20The JAK-STAT Signaling Pathway
13.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
13.8K
01:16TGF - β Signaling Pathway
10.9K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.9K