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Necrosis Factor Family (necrosis + factor_family)
Selected AbstractsDistinct expression of C1q-like family mRNAs in mouse brain and biochemical characterization of their encoded proteinsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2010Takatoshi Iijima Abstract Many members of the C1q family, including complement C1q and adiponectin, and the structurally related tumor necrosis factor family are secreted and play crucial roles in intercellular signaling. Among them, the Cbln (precerebellin) and C1q-like (C1ql) subfamilies are highly and predominantly expressed in the central nervous system. Although the Cbln subfamily serve as essential trans-neuronal regulators of synaptic integrity in the cerebellum, the functions of the C1ql subfamily (C1ql1,C1ql4) remain unexplored. Here, we investigated the gene expression of the C1ql subfamily in the adult and developing mouse brain by reverse transcriptase-polymerase chain reaction and high-resolution in-situ hybridization. In the adult brain, C1ql1,C1ql3 mRNAs were mainly expressed in neurons but weak expression was seen in glia-like structures in the adult brain. The C1ql1 mRNA was predominantly expressed in the inferior olive, whereas the C1ql2 and C1ql3 mRNAs were strongly coexpressed in the dentate gyrus. Although the C1ql1 and C1ql3 mRNAs were detectable as early as embryonic day 13, the C1ql2 mRNA was observed at later embryonic stages. The C1ql1 mRNA was also expressed transiently in the external granular layer of the cerebellum. Biochemical characterization in heterologous cells revealed that all of the C1ql subfamily proteins were secreted and they formed both homomeric and heteromeric complexes. They also formed hexameric and higher-order complexes via their N-terminal cysteine residues. These results suggest that, like Cbln, the C1ql subfamily has distinct spatial and temporal expression patterns and may play diverse roles by forming homomeric and heteromeric complexes in the central nervous system. [source] Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseasesEXPERIMENTAL DERMATOLOGY, Issue 2 2007Takashi Matsushita Abstract:, Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma. [source] Inhibition of the lymphotoxin pathway as a therapy for autoimmune diseaseIMMUNOLOGICAL REVIEWS, Issue 1 2008Jeffrey L. Browning Summary: The lymphotoxin (LT) system is part of the tumor necrosis factor family and is required for lymph node development. It has provided a wonderful tool for the dissection of processes critical not only for lymphoid organ development but also the maintenance of the adult immune architecture and the formation of ectopic organized lymphoid tissues in chronically inflamed sites. A soluble lymphotoxin-, receptor-immunoglobulin (LT,R-Ig) fusion protein can block this pathway and is currently being tested in the treatment of autoimmune disease. This review focuses on the immunological consequences of combined LT and LIGHT inhibition with LT,R-Ig administration as distinct from the developmental biology. [source] Role of cytokines of the tumour necrosis factor family in the immune response to disseminated Candida albicans infectionBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2000M. G. Netea Background Tumour necrosis factor (TNF) ,, lymphotoxin (LT) ,, CD40L and FasL are members of the TNF family that play a crucial role in modulation of the immune response. Their role in the defence against infection with Candida albicans was investigated in mice deficient in either TNF-, and LT-, (TNF,/, LT,/, mice), CD40L (CD40L,/, mice) or Fas (MRL/lpr mice). Methods Mortality rates were compared in mice infected intravenously with 106 colony-forming units of C. albicans per mouse. Results After infection with C. albicans the TNF,/, LT,/, mice had a significantly increased mortality rate compared with control mice (100 versus 40 per cent; P < 0·01). This was due to a 10,1000-fold increased outgrowth of the yeasts in the kidneys and liver of TNF,/, LT,/, mice (P < 0·01). Defective recruitment and phagocytosis, but not Candida killing, were responsible for these effects. CD40L,/, mice were also more susceptible to systemic candidiasis than the wild-type controls (mortality rate 80 versus 50 per cent; P < 0·05), and the growth of Candida in the kidneys was one order of magnitude higher in the deficient than in control mice (P < 0·05). Neutrophil function in the CD40L,/, mice was normal, whereas decreased Candida killing by macrophages through nitric oxide-dependent mechanisms was responsible for the effect of CD40/CD40L interactions. In contrast, Fas-defective MRL/lpr mice were significantly more resistant to disseminated candidiasis (mortality rate 50 versus 100 per cent; P < 0·01); this was mediated by the facilitation of neutrophil migration to the site of infection. Conclusion Cytokines of the TNF family play a crucial role in the modulation of host defence against fatal C. albicans infection. Their effects are exerted selectively at the level of neutrophil or macrophage function. © 2000 British Journal of Surgery Society Ltd [source] BAFF: a local and systemic target in autoimmune diseasesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2009I. Moisini Summary BAFF (B lymphocyte activating factor of the tumour necrosis factor family) is a vital homeostatic cytokine for B cells that helps regulate both innate and adaptive immune responses. Increased serum levels of BAFF are found in a number of different autoimmune diseases, and BAFF is found in inflammatory sites in which there is lymphoid neogenesis. BAFF antagonism has been used in several autoimmune disease models, resulting in B cell depletion, decreased activation of T cells and dendritic cells (DC) and a reduction in the overall inflammatory burden. BAFF, through its interaction with BAFF-R, is required for survival of late transitional, marginal zone and mature naive B cells, all of which are depleted by BAFF blockade. Through their interactions with TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BCMA (B cell maturation protein), BAFF and its homologue APRIL (a proliferation-inducing ligand), support the survival of at least some subsets of plasma cells; blockade of both cytokines results in a decrease in serum levels of immunoglobulin (Ig)G. In contrast, neither BAFF nor APRIL is required for the survival or reactivation of memory B cells or B1 cells. BAFF also helps DC maturation and interleukin (IL)-6 release and is required for proper formation of a follicular dendritic cell (FDC) network within germinal centres, although not for B cell affinity maturation. The clinical efficacy of BAFF blockade in animal models of autoimmunity may be caused both by the decline in the number of inflammatory cells and by the inhibition of DC maturation within target organs. Blockade of BAFF and its homologue APRIL are being explored for human use; several Phase I and II clinical trials of BAFF inhibitors for autoimmunity have been completed and Phase III trials are in progress. [source] | ||||||||||