SLE: translating lessons from model systems to human disease

Singh, Ram Raj

doi:10.1016/j.it.2005.08.013

Cited by 53 publications

(47 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Aberrant regulation of the adaptive immune response results in the production of autoantibodies that are the hallmark of both organspecific and systemic autoimmune diseases such as SLE and rheumatoid arthritis (25,26). Costimulation plays an important role in the Ag-driven immune response that lead to potentially pathogenic isotype-switched, high affinity Abs (1,11).…”

Section: Discussionmentioning

confidence: 99%

B7RP-1 Blockade Ameliorates Autoimmunity through Regulation of Follicular Helper T Cells

Metz

Chung

et al. 2009

The Journal of Immunology

121

View full text Add to dashboard Cite

Autoimmune diseases are marked by the presence of class-switched, high-affinity autoantibodies with pathogenic potential. Costimulation plays an important role in the activation of T cells and the development of T cell-dependent B cell responses. ICOS plays an indispensable role in the development of follicular helper T cells (TFH cells), which provide cognate help to germinal center (GC) B cells. We show that the levels of TFH cells and GC B cells in two different models of autoimmunity, the New Zealand Black/New Zealand White (NZB/NZW) F1 mouse model of systemic lupus erythematosus and the collagen-induced arthritis model of rheumatoid arthritis, are dependent on the maintenance of the ICOS/B7RP-1 pathway. Treatment with an anti-B7RP-1 Ab ameliorates disease manifestations and leads to a decrease in TFH cells and GC B cells as well as an overall decrease in the frequency of ICOS+ T cells. Coculture experiments of Ag-primed B cells with CXCR5+ or CXCR5− T cells show that blocking B7RP-1 does not directly impact the production of IgG by B cells. These findings further support the role of ICOS in autoimmunity and suggest that the expansion of the TFH cell pool is an important mechanism by which ICOS regulates Ab production.

show abstract

Section: Discussionmentioning

confidence: 99%

B7RP-1 Blockade Ameliorates Autoimmunity through Regulation of Follicular Helper T Cells

Metz

Chung

et al. 2009

The Journal of Immunology

121

View full text Add to dashboard Cite

show abstract

“…In some cases, autoantibodies are directed to a cell-surface receptor, such as the acetylcholine receptor in myasthenia gravis or the thyroid stimulating hormone receptor in Grave's disease (Kohn and Harii, 2003;Vincent, 2002). Antibodies can also form immune complexes with circulating autoantigens, which accumulate in the kidneys and joint synovium in patients with SLE and RA (Davidson and Aranow, 2006;Dorner et al, 2004;Rahman and Isenberg, 2008;Singh, 2005). Other autoantibodies bind to circulating cells such as platelets or erythrocytes, triggering complement-mediated lysis or phagocytosis by Fc-receptor bearing cells (Elson and Barker, 2000).…”

Section: Autoantibody Production By B Cellsmentioning

confidence: 99%

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

McLaughlin

Wucherpfennig

2008

Advances in Immunology

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The mainstream view is that MS is caused by an autoimmune attack of the CNS myelin by myelin-specific CD4 T cells, and this perspective is supported by extensive work in the experimental autoimmune encephalomyelitis (EAE) model of MS as well as immunological and genetic studies in humans. However, it is important to keep in mind that other cell populations of the immune system are also essential in the complex series of events leading to MS, as exemplified by the profound clinical efficacy of B cell depletion with Rituximab. This review discusses the mechanisms by which B cells contribute to the pathogenesis of MS and dissects their role as antigen-presenting cells (APCs) to T cells with matching antigen specificity, the production of proinflammatory cytokines and chemokines, as well as the secretion of autoantibodies that target structures on the myelin sheath and the axon. Mechanistic dissection of the interplay between T cells and B cells in MS may permit the development of B cell based therapies that do not require depletion of this important cell population.

show abstract

“…The p300 gene does not map to a known SLE susceptibility or suppressor locus in humans or mice. However, SLE is a highly heterogeneous disease, and mice with reduced p300 AT activity may model a subgroup of human SLE whose genetic basis cannot be revealed by linkage analysis (50,51). Alternatively, analogous to the situation in cancer, reduced protein acetylation may be a common downstream event in human SLE, regardless of the primary genetic defect.…”

Section: Discussionmentioning

confidence: 99%

p300 Protein Acetyltransferase Activity Suppresses Systemic Lupus Erythematosus-Like Autoimmune Disease in Mice

Forster

Gallinat

Jabłońska

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Conditional knock-in mice expressing a histone acetyltransferase-deficient version of the transcriptional coregulator p300 exclusively in B lymphocytes die prematurely with full penetrance. The mice develop an autoimmune disease similar to systemic lupus erythematosus in its pathological manifestations, such as splenomegaly, glomerulonephritis, vasculitis, deposition of immune complexes, and production of autoantibodies against dsDNA. Aged mice show a severe reduction of transitional and marginal zone B cells and generate aberrant mature B cells. These B cells show diminished proliferation in response to stimulation of the BCR, but respond normally to other stimuli. Yet, the mice mount a normal primary immune response against a T-dependent Ag. In contrast, the memory response is impaired. In addition, serum Ig levels, in particular IgG2b, are increased. We conclude that p300 acetyltransferase activity is essential for maintaining self-tolerance of B lymphocytes. These findings support the concept of treating lupus with inhibitors of protein deacetylases and point to B cells as a critical target of these drugs.

show abstract

SLE: translating lessons from model systems to human disease

Cited by 53 publications

References 64 publications

B7RP-1 Blockade Ameliorates Autoimmunity through Regulation of Follicular Helper T Cells

B7RP-1 Blockade Ameliorates Autoimmunity through Regulation of Follicular Helper T Cells

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

p300 Protein Acetyltransferase Activity Suppresses Systemic Lupus Erythematosus-Like Autoimmune Disease in Mice

Contact Info

Product

Resources

About