Cutting Edge: Slamf8 Is a Negative Regulator of Nox2 Activity in Macrophages

Wang, Guoxing; Abadía-Molina, Ana Clara; Berger, Scott B.; Romero, Xavier; O’Keeffe, Michael; Rojas-Barros, Domingo I.; Aleman, Marta; Liao, Guojun; Maganto-García, Elena; Fresno, Manuel; Wang, Ninghai; Detre, Cynthia; Terhorst, Cox

doi:10.4049/jimmunol.1102620

Cited by 41 publications

(66 citation statements)

References 11 publications

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“…22 SLAMF8 (Slam family member 8) is a macrophage activation marker also induced by interferon γ. 30 Thus, upregulation of SLAMF8 fits well with the current understanding of the pathogenesis of sarcoidosis. Several other transcripts that we found to be upregulated in the orbit in tissue from patients with sarcoidosis have been implicated in studies on sarcoidosis in other tissues, including Fcγ receptor 1 (CD64 [OMIM 147840]), 37 ICAM-1 (OMIM 146760), 38 and IL-1β (OMIM 147720).…”

Section: Discussionsupporting

confidence: 71%

“…We compared the list of probe sets identified in the blood study using the same selection criteria as described above with the list of probe sets with increased signals in both the lacrimal gland (eTable 3 in the Supplement) and orbital adipose (eTable 1 in the Supplement) tissue and found 92 probe sets (OMIM 147796) in common (Table 4 and eTable 5 in the Supplement). Several of these genes are associated with interferon responses (eg, CXCL10 [OMIM 14731], 22 GBP5 [OMIM 611467], 23 STAT1 [OMIM 600555], 24 TGM2 [OMIM 190196], 25 AIM2 [OMIM 604578], 26 WARS [OMIM 191050], 27 ICAM1 [OMIM 147840], 28 TNFAIP2 [OMIM 603300], 29 SLAMF8 [OMIM 606620], 30 and JAK2 [OMIM 147796] 31 ). Similarly, there were 67 probe sets with decreased signals in peripheral blood in the prior report 7 and in both orbital adipose tissue and lacrimal gland in the present study (eTable 6 in the Supplement).…”

Section: Resultsmentioning

confidence: 99%

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Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

et al. 2015

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IMPORTANCE Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy.OBJECTIVE To determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis. DESIGN, SETTING, AND PARTICIPANTSIn a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis. MAIN OUTCOMES AND MEASURESSignificantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P < .05.RESULTS Signals from 2449 probe sets (transcripts from approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and 67 probe sets (approximately 56 genes) had significantly lower signals in both orbital tissues and in peripheral blood from patients with sarcoidosis. The transcription factors, interferon-response factor 1, interferon-response factor 2, and nuclear factor κB, were strongly implicated in the expression of messenger RNA upregulated in common in the 3 tissues.CONCLUSIONS AND RELEVANCE Gene expression in sarcoidosis involving the orbit or lacrimal gland can be distinguished from gene expression patterns in control tissue and overlaps with many transcripts upregulated or downregulated in the peripheral blood of patients with sarcoidosis. These observations suggest that common pathogenic mechanisms contribute to sarcoidosis in different sites. The observations support the hypothesis that a pattern of gene expression profiles could provide diagnostic information in patients with sarcoidosis.

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Section: Discussionsupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

et al. 2015

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“…Other SLAM family members without cytoplasmic ITSMs are able to signal without direct modification by tyrosine kinases. Although CD48 functions as the ligand for CD244 (2B4/SLAMF4), it can signal through its association with lipid rafts, and homotypic interactions by BLAME influence cellular function through unknown mechanisms …”

Section: Discussionmentioning

confidence: 99%

“…In addition to these functions, SLAM family receptors have been directly implicated in pathogen recognition and clearance by macrophages. For example, SLAM contributes to recognition of Gram‐negative bacteria, and BLAME regulates the production of reactive oxygen species …”

Section: Introductionmentioning

confidence: 99%

Signalling lymphocyte activation molecule family member 9 is found on select subsets of antigen‐presenting cells and promotes resistance to Salmonella infection

et al. 2020

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Summary Signalling lymphocyte activation molecule family member 9 (SLAMF9) is an orphan receptor of the CD2/SLAM family of leucocyte surface proteins. Examination of SLAMF9 expression and function indicates that SLAMF9 promotes inflammation by specialized subsets of antigen‐presenting cells. Within healthy liver and circulating mouse peripheral blood mononuclear cells, SLAMF9 is expressed on CD11b+, Ly6C−, CD11clow, F4/80low, MHC‐II+, CX3CR1+ mononuclear phagocytes as well as plasmacytoid dendritic cells. In addition, SLAMF9 can be found on peritoneal B1 cells and small (F4/80low), but not large (F4/80high), peritoneal macrophages. Upon systemic challenge with Salmonella enterica Typhimurium, Slamf9−/− mice were impaired in their ability to clear the infection from the liver. In humans, SLAMF9 is up‐regulated upon differentiation of monocytes into macrophages, and lipopolysaccharide stimulation of PMA‐differentiated, SLAMF9 knockdown THP‐1 cells showed an essential role of SLAMF9 in production of granulocyte–macrophage colony‐stimulating factor, tumour necrosis factor‐α, and interleukin‐1β. Taken together, these data implicate SLAMF9 in the initiation of inflammation and clearance of bacterial infection.

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“…The discriminatory impact of increased expression of these genes identified in our analysis, however, suggests that there are distinct differences during the responses to these very different pathogens sufficient to discriminate underlying disease aetiology (Munoz‐Jordan et al , ; Obiero et al , ) possibly based on subtle metabolic differences (Zhang et al , ; Blohmke et al , ). While STAT1 and WARS are markers of an IFN‐γ response, SLAMF8 is a surface‐expressed protein (van Driel et al , ) found on macrophages, DCs and neutrophils and induced by IFN‐γ or Gram‐negative bacteria (Wang et al , ). SLAMF8 negatively regulates ROS production through inhibition of NADPH oxidase 2 (NOX2) in the bacterial phagosome and reduces ROS‐induced inflammatory cell migration (Wang et al , ).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic host gene signature for distinguishing enteric fever from other febrile diseases

et al. 2019

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Misdiagnosis of enteric fever is a major global health problem, resulting in patient mismanagement, antimicrobial misuse and inaccurate disease burden estimates. Applying a machine learning algorithm to host gene expression profiles, we identified a diagnostic signature, which could distinguish culture‐confirmed enteric fever cases from other febrile illnesses (area under receiver operating characteristic curve > 95%). Applying this signature to a culture‐negative suspected enteric fever cohort in Nepal identified a further 12.6% as likely true cases. Our analysis highlights the power of data‐driven approaches to identify host response patterns for the diagnosis of febrile illnesses. Expression signatures were validated using qPCR, highlighting their utility as PCR‐based diagnostics for use in endemic settings.

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Cutting Edge: Slamf8 Is a Negative Regulator of Nox2 Activity in Macrophages

Cited by 41 publications

References 11 publications

Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

Signalling lymphocyte activation molecule family member 9 is found on select subsets of antigen‐presenting cells and promotes resistance to Salmonella infection

Diagnostic host gene signature for distinguishing enteric fever from other febrile diseases

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