T-cells in the pathogenesis of rheumatoid arthritis Villains or accomplices?

Kinne, Raimund W.; Palombo‐Kinne, Ernesta; Emmrich, Frank

doi:10.1016/s0925-4439(96)00079-8

Cited by 53 publications

(49 citation statements)

References 309 publications

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“…The main characteristics of RA is the dense lymphoid infiltration into the synovial membrane associated with juxtaarticular bone loss occurring around inflamed joints and a generalized bone loss with reduced bone mass [reviewed in Gough et al, 1994;Dequeker et al, 1995;Deodhar and Woolf, 1996]. However, RA is also considered a systemic disease which includes serological and hematological signs of inflammation, subcutaneous rheumatoid nodules, high levels of circulating rheumatoid factor, vasculitis, and granulomatous and/or interstitial organ pathologies [Kinne et al, 1997]. Of interest is the fact that 70-80% of RA patients display an association with HLA-DR or HLA-DQ loci of the MHC-II complexes, with predominance of certain alleles that act as independent susceptibility genes.…”

mentioning

confidence: 99%

“…Of interest is the fact that 70-80% of RA patients display an association with HLA-DR or HLA-DQ loci of the MHC-II complexes, with predominance of certain alleles that act as independent susceptibility genes. The presence of these MHC-II complexes is the most compelling evidence to support the concept that T cell recognition is important at some stage in the pathogenesis of RA, either in shaping the T cell receptor (TCR) or in the presentation of an inducing autoantigenic peptide via an antigen presenting cell [Kinne et al, 1997]. In untreated RA patients, serum markers of bone formation (osteocalcin (OCN) and bone-specific alkaline phosphatase) and urinary markers of bone resorption (procollagen type I C-terminal telopeptide, pyridinoline and deoxypyridinoline, and hydroxyproline excretion) are significantly higher than those of control patients [Gough et al, 1994;Hanna et al, 1997;Suzuki et al, 1998].…”

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confidence: 99%

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Inflammatory T cells rapidly induce differentiation of human bone marrow stromal cells into mature osteoblasts

Rifas

Arackal

Weitzmann

2003

J of Cellular Biochemistry

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Activated T cells secrete multiple osteoclastogenic cytokines which play a major role in the bone destruction associated with rheumatoid arthritis. While the role of T cells in osteoclastogenesis has received much attention recently, the effect of T cells on osteoblast formation and activity is poorly defined. In this study, we investigated the hypothesis that in chronic inflammation activated T cells contribute to enhanced bone turnover by promoting osteoblastic differentiation. We show that T cells produce soluble factors that induce alkaline phosphatase activity in bone marrow stromal cells and elevated expression of mRNA for Runx2 and osteocalcin. This data indicate that T cell derived factors have the capacity to stimulate the differentiation of bone marrow stromal cells into the osteoblast phenotype. RANKL mRNA was undetectable under any conditions in highly purified bone marrow stromal cells. In contrast, RANKL was constitutively expressed in primary osteoblasts and only moderately up-regulated by activated T cell conditioned medium. Interestingly, both bone marrow stromal cells and osteoblasts expressed mRNA for RANK, which was strongly up-regulated in both cell types by activated T cell conditioned medium. Although, mRNA for the RANKL decoy receptor, osteoprotegerin, was also up-regulated by activated T cell conditioned medium, it's inhibitory effects may be mitigated by a simultaneous rise in the osteoprotegerin competitor TNF-related apoptosis-inducing ligand. Based on our data we propose that during chronic inflammation, T cells regulate bone loss by a dual mechanism involving both direct stimulation of osteoclastogenesis, by production of osteoclastogenic cytokines, and indirectly by induction of osteoblast differentiation and up-regulation of bone turnover via coupling.

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confidence: 99%

mentioning

confidence: 99%

Inflammatory T cells rapidly induce differentiation of human bone marrow stromal cells into mature osteoblasts

Rifas

Arackal

Weitzmann

2003

J of Cellular Biochemistry

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“…These early studies of autoimmunity to collagen were performed before there was clear distinction between type II collagen in articular cartilage, first described by Miller [14], and type I collagen in skin and bone, a problem that made the interpretation of some earlier studies difficult. Nonetheless, serum and synovial fluid of patients with RA have repeatedly been shown to display antibody [15][16][17] and T cell reactivity to CII [18][19][20][21] and autoantibodies to other cartilage collagens [22] as well. In early RA, serum autoantibodies to CII are present in up to 70% of cases [15,16,23,24], but there is a rapid decline in the frequencies and levels of such antibodies among patients with erosive disease [25], possibly because these antibodies become sequestered in immune complexes within the joint as the cartilage is progressively eroded, thus exposing collagen.…”

Section: Autoimmunity To Collagen In Rheumatoid Arthritismentioning

confidence: 99%

The role of collagen antibodies in mediating arthritis

2008

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This review examines evidence that rheumatoid arthritis (RA) depends on autoimmunity to articular collagen, and mechanisms whereby autoantibodies to type II collagen contribute to disease development. Three major autoantigenic reactants have been identified in RA; the corresponding autoantibodies are rheumatoid factor (RF), antibodies to citrullinated peptide antigens (ACPA), citrullinated peptides (anti-CCP), and anti-type II collagen (anti-CII). Both RF and ACPA are well-validated and predictive markers of severe erosive RA, but cannot be linked to pathogenesis. By contrast, in various animal species immunized with CII there occurs an erosive inflammatory arthritis resembling that seen in human RA, together with antibodies to CII with an epitope specificity similar to that in RA. We discuss the well-known role of immune complexes in the induction of inflammation within the joint, and present recent data showing, additionally, that antibodies to CII cause direct damage to cartilage in vitro. The close resemblances between human RA and collagen-induced arthritis in animals suggest that autoimmunity, and particularly autoantibodies to CII, are important for both the initiation and perpetuation of RA in a dual manner: as contributors to the inflammation associated with immune complex deposition, and as agents with direct degradative effects on cartilage integrity and its repair.

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“…In fact, the synovial tissue of RA patients is characterized by predominant T cell infiltrates, including both CD4ϩ and CD8ϩ subsets. Eighty percent of the lymphatic infiltrates in the lower layer of the inflamed synovium consists of T cells that are organized in follicle-like cell structures (26,27).…”

Section: Fls With T Helper Cell Subsets Effects Of Mif Were Blocked mentioning

confidence: 99%

Interactions of T helper cells with fibroblast‐like synoviocytes: Up‐regulation of matrix metalloproteinases by macrophage migration inhibitory factor from both Th1 and Th2 cells

Schurigt¹,

Pfirschke²,

Irmler³

et al. 2008

Arthritis & Rheumatism

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Conclusion. MIF is an important Th1 and Th2 cell-derived proinflammatory cytokine that stimulates MMP expression in FLS from arthritic mice, and therefore inhibition of MIF might be a promising target for novel therapeutic strategies in human RA.Macrophage migration inhibitory factor (MIF) is a structurally unique cytokine that is a critical mediator of several acute and chronic inflammatory diseases. Of note, MIF has been prominently detected in supernatants of T cells and in macrophages (1-5). Although it was originally described as a soluble factor that inhibits the undirected migration of macrophages, an effect known to participate in delayed-type hypersensitivity reactions (1,6), it has become evident that MIF functions in a chemokine-like manner to trigger the directed migration of leukocytes, an effect that involves CXCR2 ligation and the induction of monocyte chemoattractant protein 1 release by endothelial cells (7,8).

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T-cells in the pathogenesis of rheumatoid arthritis Villains or accomplices?

Cited by 53 publications

References 309 publications

Inflammatory T cells rapidly induce differentiation of human bone marrow stromal cells into mature osteoblasts

Inflammatory T cells rapidly induce differentiation of human bone marrow stromal cells into mature osteoblasts

The role of collagen antibodies in mediating arthritis

Interactions of T helper cells with fibroblast‐like synoviocytes: Up‐regulation of matrix metalloproteinases by macrophage migration inhibitory factor from both Th1 and Th2 cells

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