Inherited Human Caspase 10 Mutations Underlie Defective Lymphocyte and Dendritic Cell Apoptosis in Autoimmune Lymphoproliferative Syndrome Type II

Wang, Jin; Zheng, Lixin; Lobito, Adrian A.; Chan, Francis Ka Ming; Dale, Janet K.; Sneller, Michael C.; Xu, Yao; Puck, Jennifer M.; Straus, Stephen E.

doi:10.1016/s0092-8674(00)80605-4

Cited by 580 publications

(371 citation statements)

References 66 publications

(4 reference statements)

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“…Supporting this idea, there are an increased frequency and number of DCs in lpr/lpr mice. In this regard, it is intriguing that a defect in another apoptosis-related gene, caspase 10, resulted in an accumulation of DCs in the T cell zone of the lymph node of one patient with autoimmune lymphoproliferative syndrome type II (71). Another possibility arises from the recent suggestion that Fas is not a death receptor for DCs, but rather acts to induce their maturation (50).…”

Section: Discussionmentioning

confidence: 99%

Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells

Fields

Sokol

Eaton-Bassiri

et al. 2001

The Journal of Immunology

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Autoantibodies directed against dsDNA are found in patients with systemic lupus erythematosus as well as in mice functionally deficient in either Fas or Fas ligand (FasL) (lpr/lpr or gld/gld mice). Previously, an IgH chain transgene has been used to track anti-dsDNA B cells in both nonautoimmune BALB/c mice, in which autoreactive B cells are held in check, and MRL-lpr/lpr mice, in which autoantibodies are produced. In this study, we have isolated the Fas/FasL mutations away from the autoimmune-prone MRL background, and we show that anti-dsDNA B cells in Fas/FasL-deficient BALB/c mice are no longer follicularly excluded, and they produce autoantibodies. Strikingly, this is accompanied by alterations in the frequency and localization of dendritic cells as well as a global increase in CD4 T cell activation. Notably, as opposed to MRL-lpr/lpr mice, BALB-lpr/lpr mice show no appreciable kidney pathology. Thus, while some aspects of autoimmune pathology (e.g., nephritis) rely on the interaction of the MRL background with the lpr mutation, mutations in Fas/FasL alone are sufficient to alter the fate of anti-dsDNA B cells, dendritic cells, and T cells.

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Section: Discussionmentioning

confidence: 99%

Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells

Fields

Sokol

Eaton-Bassiri

et al. 2001

The Journal of Immunology

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“…The cognate ligand for Fas (FasL) is an activation antigen expressed by CD4+ Th1 effector cells and CD8 cytotoxic T lymphocytes, (although its activity in the latter is frequently masked by the more substantial destructive power of the perforin-granzyme system), as well as natural killer cells [8][9][10][11][12][13]. The congenital loss of Fas (as in lpr/lpr mice and Fas null mice, and in human Autoimmune Lymphoproliferation Syndrome) or of its ligand (as in gld/gld mice) is accompanied by severely elevated levels of serum autoantibodies associated with frank autoimmunity [14][15][16][17][18][19][20][21][22][23][24]; for this reason Fas is thought to play a key role in the regulation of B cells, particularly in the regulation of autoreactive B cells. These observations are supported and refined by additional experiments, carried out over the last dozen years, that more clearly document abnormal B cell function in Fas-deficient animals and distinguish B cell defects from abnormalities in the T cell population.…”

Section: Inroductionmentioning

confidence: 99%

Inducible resistance to Fas-mediated apoptosis in B cells

Rothstein

2000

Cell Res

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Apoptosis produced in B cells through Fas (APO-1, CD95) triggering is regulated by signals derived from other surface receptors: CD40 engagement produces upregulation of Fas expression and marked susceptibility to Fas-induced cell death, whereas antigen receptor engagement, or IL-4R engagement, inhibits Fas killing and in so doing induces a state of Fas-resistance, even in otherwise sensitive, CD40-stimulated targets. Surface immunoglobulin and IL-4R utilize at least partially distinct pathways to produce Fas-resistance that differentially depend on PKC and STAT6, respectively. Further, surface immunoglobulin signaling for inducible Fas-resistance bypasses Btk, requires NF-κB, and entails new macromolecular synthesis. Terminal effectors of B cell Fas-resistance include the known anti-apoptotic gene products, Bcl-xL and FLIP, and a novel anti-apoptotic gene that encodes FAIM (Fas Apoptosis Inhibitory Molecule). faim was identified by differential display and exists in two alter-

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“…The clinical characteristics are lymphoadenopathy, splenomegaly, polygammaglobulinemia, and SLE-like systemic autoimmunity. [15][16][17][18] Abnormal expression of FasL on lymphocytes and apoptosis triggering has been demonstrated in SLE patients. [19][20][21][22] Anti-FasL antibody, which inhibits Fas/FasL-mediated apoptosis, can be detected in SLE patients.…”

Section: Introductionmentioning

confidence: 99%

The −844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE

Chen¹,

Wang²,

Chi³

et al. 2005

Genes Immun

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FasL expression is critical in T-cell activation-induced apoptosis, which is involved in lupus pathogenesis. This study identified two SNPs in the FasL promoter regions from -1145 to -45 by genomic DNA sequencing. The -844C/T polymorphism was previously described by its location in and affect on the CCAAT/enhancer-binding protein b (C/EBPB b)-binding site and the other (-1094A/C, a novel polymorphism) was located at the NF-kB transcription-binding site. FasL gene promoter polymorphisms were genotyped in 260 systemic lupus erythematosus (SLE) patients and 280 healthy controls using MassArray matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. The distribution of FasL promoter -844C/C genotype, predominant in Taiwanese, was skewed in Taiwanese SLE patients (odds ratio: 1.53; P-value ¼ 0.014). FasL promoter À844C/T polymorphism genotype distributions of Taiwanese, African Americans, and Caucasians differed. Moreover, no particular clinical association of À844C/T and À1094A/C polymorphisms with SLE was found in patients in Taiwan. This study confirmed that À844C/C genotype is associated with lupus susceptibility. The -1094A/C polymorphism is not significantly associated with lupus disease susceptibility, albeit the role of NF-kB pathway in FasL promoter activation remains unclear. Fas/FasL pathway may contribute to SLE polygenic disease entity.

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Inherited Human Caspase 10 Mutations Underlie Defective Lymphocyte and Dendritic Cell Apoptosis in Autoimmune Lymphoproliferative Syndrome Type II

Cited by 580 publications

References 66 publications

Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells

Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells

Inducible resistance to Fas-mediated apoptosis in B cells

The −844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE

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