Characterization of a New Member of the TNF Family Expressed on Antigen Presenting Cells

Tribouley, Catherine; Wallroth, Marco; Chan, Vinson Wai‐Shun; Paliard, Xavier; Fang, Evandro Fei; Lamson, George; Pot, David; Escobedo, José Jesús Muñoz; Lt, Williams

doi:10.1515/bc.1999.186

Cited by 92 publications

(53 citation statements)

References 10 publications

(9 reference statements)

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“…2E), we hypothesized that this cell type might have a role in the defective TLR7-induced Ab response of MS patients through the release of cytokines involved in B-cell differentiation and activation, such as IL-6 and BAFF [25][26][27].…”

Section: Monocytes Have a Key Role In Tlr7-stimulated B-cell Differenmentioning

confidence: 99%

IFN‐β therapy modulates B‐cell and monocyte crosstalk via TLR7 in multiple sclerosis patients

et al. 2013

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The implication of B lymphocytes in the immunopathology of multiple sclerosis (MS) is increasingly recognized. Here we investigated the response of B cells to IFN-β, a first-line therapy for relapsing-remitting MS patients, upon stimulation with TLR. IFN-β restored the frequency of TLR7-induced IgM and IgG-secreting cells in MS patients to the levels found in healthy donors, showing a specific deficiency in the TLR7 pathway. However, no difference was observed in the TLR9 response. Furthermore, in MS-derived PBMCs, TLR7-mediated production of IL-6 and the ex vivo expression of B-cell-activating factor of the TNF family, two crucial cytokines for B-cell differentiation and survival, were induced by IFN-β. Depletion of monocytes, which are key producers of both IL-6 and B-cellactivating factor of the TNF family, showed that TLR7-mediated B-cell differentiation into Ig-secreting cells is strongly dependent on the cross-talk between B cells and monocytes. Accordingly, impaired expression of TLR7 mRNA was observed in PBMCs and monocytes isolated from MS-affected individuals as compared with those from healthy donors, which was rescued by IFN-β therapy. Collectively, our data unveil a novel TLR7-regulated mechanism in in vivo IFN-β-stimulated whole leukocytes that could be exploited to define new TLR7-based strategies for the treatment of MS.Keywords: B cell r IFN-β r Monocyte r Multiple sclerosis r TLR Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionGrowing evidence is accumulating on the central role that B lymphocytes play in the immunopathology of multiple sclerosis (MS) [1,2]. For example, oligoclonal IgG bands, found in the cerebrospinal fluid of more than 90% of patients with MS, indicate an intrathecal Ab production [3]. The presence of clonally Correspondence: Dr. Eliana Marina Coccia e-mail: eliana.coccia@iss.it expanded B cells, plasma cells, complement and myelin-specific Abs in chronic MS lesions also suggested an intrathecal, Agdriven humoral immune response in the central nervous system of MS sufferers [4][5][6]. In addition, B-cell follicle-like structures are detectable in the meninges of MS patients [7,8]. More recently, B-cell depleting therapies, such as Rituximab (that targets the B lymphocyte surface antigen CD20 [9][10][11]), together with * These authors contributed equally to this work. Eur. J. Immunol. 2013Immunol. . 43: 1963Immunol. -1972 Ocrelizumab and Ofatumumab (two other humanized anti-CD20 monoclonal Abs), are proving their efficacy at various stages of clinical development [12]. All together these findings contribute to the compelling evidence that B cells and the humoral immune response are implicated in the pathogenesis of MS and suggest the therapeutic implications that all this may have for the treatment of this disease. B lymphocytes play an essential role in bridging innate and adaptive immunity. To differentiate into specialized cells capable of communicating with helper T cells and undergo Ab divers...

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Section: Monocytes Have a Key Role In Tlr7-stimulated B-cell Differenmentioning

confidence: 99%

IFN‐β therapy modulates B‐cell and monocyte crosstalk via TLR7 in multiple sclerosis patients

et al. 2013

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“…BAFF, also known as B lymphocyte stimulator (BLyS), TALL-1, THANK, tumor necrosis factor superfamily member 13B, and zTNF4, is a 285-amino acid type II transmembrane protein member of the tumor necrosis factor ligand superfamily (1)(2)(3)(4)(5)(6). It is expressed by myeloid lineage cells (1)(2)(3)5,7,8), bone marrowderived radiation-resistant stromal cells (9), and T cells (10), and it is cleaved at the cell surface by a furin protease to release a soluble, biologically active 17-kd molecule (1,7).…”

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confidence: 99%

BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus

Stohl¹,

Xu²,

Kim³

et al. 2005

Arthritis & Rheumatism

104

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Objective. To determine whether overexpression of BAFF can accelerate the development of systemic lupus erythematosus-associated end-organ disease in hosts with an underlying autoimmune diathesis.Methods. We introduced a BAFF transgene (Tg) into autoimmune-prone B6.Sle1 and B6.Nba2 mice and evaluated these mice for serologic autoimmunity and renal pathology.Results Conclusion. BAFF-driven effects on glomerular pathology may be mediated, at least in part, by autoantibodies with specificities other than chromatin and/or by autoantibody-independent means. There is an uncoupling of BAFF-driven precocious glomerular pathology from concomitant development of clinically apparent renal disease, strongly suggesting that BAFF overexpression works in concert with other factors to promote overt renal disease.Renal involvement in patients with systemic lupus erythematosus (SLE) is clinically apparent in ϳ50% of cases and leads to considerable morbidity. The vast majority of SLE patients with renal involvement develop increased proteinuria, sometimes to degrees great enough to adversely affect systemic fluid balance and hemodynamics (nephrotic syndrome). Glomerular disease is widely believed to be the major contributor to this increased proteinuria. Indeed, the World Health Organization (WHO) classification of lupus nephritis focuses almost entirely on glomerular lesions, with little attention to tubular, interstitial, or vascular lesions. Accordingly, factors which promote glomerular disease in SLE may be vital to the pathogenesis of lupus nephritis.

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“…B lymphocyte stimulator (BLyS; trademark of Human Genome Sciences, Rockville, MD) protein is a recently identified 285-amino acid member of the tumor necrosis factor (TNF) ligand superfamily (1)(2)(3)(4)(5)(6). Other names for this protein are TALL-1, BAFF, THANK, TNFSF20 (subsequently renamed TNFSF13B), and zTNF4.…”

mentioning

confidence: 99%

“…Other names for this protein are TALL-1, BAFF, THANK, TNFSF20 (subsequently renamed TNFSF13B), and zTNF4. It is expressed as a type II transmembrane protein, which is cleaved from the cell surface to release a biologically active soluble 17-kd protein (1)(2)(3)(4)(5). Mice genetically deficient in BLyS protein harbor markedly reduced numbers of mature B cells in secondary lymphoid organs and manifest reduced baseline serum levels of Ig and Ig responses to T cell-dependent and T cell-independent antigens (7,8).…”

mentioning

confidence: 99%

Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis

Tan

Roschke

et al. 2003

Arthritis & Rheumatism

189

144

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Objective. To determine whether synovial fluid (SF) levels and cell-surface expression of B lymphocyte stimulator (BLyS) protein and SF levels of APRIL are elevated in patients with inflammatory arthritis (IA).Methods. Results. BLyS protein levels were higher in SF than in corresponding serum samples from both IA and NIA patients. SF BLyS protein levels, but not surface expression of BLyS protein, were disproportionately elevated in IA patients. APRIL levels were higher in SF than in corresponding serum samples from most IA patients but not NIA patients. SF BLyS protein and APRIL levels correlated with each other, and each correlated with SF monocyte, lymphocyte, neutrophil, and total nucleated cell counts. Although SF and serum BLyS protein levels correlated with each other, SF and serum APRIL levels did not, suggesting that SF BLyS protein levels are more dependent upon systemic factors than are SF APRIL levels. Moreover, in 8 patients who underwent sequential arthrocenteses, changes in SF BLyS protein levels did not immutably parallel changes in SF APRIL levels, indicating their differential regulation.Conclusion. BLyS protein and APRIL are locally produced in inflamed joints. Their respective SF levels are differentially regulated, suggesting that they serve different functions. Together, their local production may foster survival and/or expansion of B cells that produce pathogenic autoantibodies and/or promote local T cell activation and consequent joint destruction.

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Characterization of a New Member of the TNF Family Expressed on Antigen Presenting Cells

Cited by 92 publications

References 10 publications

IFN‐β therapy modulates B‐cell and monocyte crosstalk via TLR7 in multiple sclerosis patients

IFN‐β therapy modulates B‐cell and monocyte crosstalk via TLR7 in multiple sclerosis patients

BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus

Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis

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