The apoptosis modulating role of SAP (SLAM associated protein) contributes to the symptomatology of the X linked lymphoproliferative disease

Nagy, Noémi; Matskova, Liudmila; Hellman, Ulf; Klein, George; Klein, Eva

doi:10.4161/cc.8.19.9636

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…Evidence from previous studies suggested that SAP deficiency could lead to the inhibition of NK cytotoxicity in humans [28], [55]–[56]. It has also been shown that in the absence of SAP, lymphoma development would normally be eliminated by apoptosis in patients with X-linked lymphoproliferative disease [57]. However, the analysis of potential apoptosis caused by reducing expression of SAP indicated that the deficiency of SAP would not lead to the significant apoptosis of NK92 cells (Data not show).…”

Section: Discussionmentioning

confidence: 77%

TGF-β1 Down-Regulation of NKG2D/DAP10 and 2B4/SAP Expression on Human NK Cells Contributes to HBV Persistence

et al. 2012

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The mechanism underlying persistent hepatitis B virus (HBV) infection remains unclear. We investigated the role of innate immune responses to persistent HBV infection in 154 HBV-infected patients and 95 healthy controls. The expression of NKG2D- and 2B4-activating receptors on NK cells was significantly decreased, and moreover, the expression of DAP10 and SAP, the intracellular adaptor proteins of NKG2D and 2B4 (respectively), were lower, which then impaired NK cell-mediated cytotoxic capacity and interferon-γ production. Higher concentrations of transforming growth factor-beta 1 (TGF-β1) were found in sera from persistently infected HBV patients. TGF-β1 down-regulated the expression of NKG2D and 2B4 on NK cells in our in vitro study, leading to an impairment of their effector functions. Anti-TGF-β1 antibodies could restore the expression of NKG2D and 2B4 on NK cells in vitro. Furthermore, TGF-β1 induced cell-cycle arrest in NK cells by up-regulating the expression of p15 and p21 in NK cells from immunotolerant (IT) patients. We conclude that TGF-β1 may reduce the expression of NKG2D/DAP10 and 2B4/SAP, and those IT patients who are deficient in these double-activating signals have impaired NK cell function, which is correlated with persistent HBV infection.

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Section: Discussionmentioning

confidence: 77%

TGF-β1 Down-Regulation of NKG2D/DAP10 and 2B4/SAP Expression on Human NK Cells Contributes to HBV Persistence

et al. 2012

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“…Higher levels of SAP can interact with Valosin-containing protein (VCP/p97) and may interfere with NFκB signaling. 5,22 To test the involvement of p53 in regulating SAP levels in activated T cells, we used Nutlin-3 to specifically induce p53 accumulation and p53 transcription activity. Nutlin-3 treatment of non-activated T cells for 6 h resulted in upregulation of SAP mRNA along with other known p53-responsive genes, i.e., p21 and Bax, 23 which is consistent with SAP being a transcription target of p53.…”

Section: Separation Activation and Treatment Of Primary T Cellmentioning

confidence: 99%

p53 contributes to T cell homeostasis through the induction of pro-apoptotic SAP

et al. 2012

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“…Pathogenic NLRC4 variants render constitutive NLRC4 inflammasome activation driving high levels of IL-1β and most importantly IL-18 that results in macrophage activation/HLH phenotype [22,23]. Patients with X-linked lymphoproliferative syndromes (SH2DIA, BIRC4 and XIAP) characteristically associated with increased susceptibility to infection with Epstein Barr virus, dysgammaglobulinemia and lymphoma can also develop life-threatening HLH [24,25]. Among immune dysregulation group, syndromes with autoimmunity or immune dysregulation with colitis are included.…”

Section: Diseases Of Immune Dysregulationmentioning

confidence: 99%

Functional Genetics in Inborn Errors of Immunity

Rey-Jurado

Poli

2021

Future Rare Dis.

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Inborn errors of immunity are genetic defects of the immune system, causing increased susceptibility to infection, autoinflammation, autoimmunity and immune dysregulation. Next-generation sequencing has enabled exponential identification of novel inborn errors of immunity due to mutations in genes encoding for proteins that participate in the immune response. However, genomic sequencing often yields multiple variants in potential candidate genes, hence functional validation of these genetic defects becomes paramount to achieve diagnosis and discovery. Genome-editing technologies such as CRISPR-Cas9 have allowed exponential advances on discovery of new primary immunodeficiencies, enabling appropriate diagnosis and treatment. This review summarizes the heterogeneous clinical presentation of primary immunodeficiencies and contextualizes the rationale for functional validation studies to achieve diagnosis and discovery, subsequently leading to the application of directed therapies.

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The apoptosis modulating role of SAP (SLAM associated protein) contributes to the symptomatology of the X linked lymphoproliferative disease

Cited by 7 publications

References 41 publications

TGF-β1 Down-Regulation of NKG2D/DAP10 and 2B4/SAP Expression on Human NK Cells Contributes to HBV Persistence

TGF-β1 Down-Regulation of NKG2D/DAP10 and 2B4/SAP Expression on Human NK Cells Contributes to HBV Persistence

p53 contributes to T cell homeostasis through the induction of pro-apoptotic SAP

Functional Genetics in Inborn Errors of Immunity

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