Macrophage Scavenger Receptor 1 (Msr1, SR-A) Influences B Cell Autoimmunity by Regulating Soluble Autoantigen Concentration

Haasken, Stefanie; Auger, Jennifer L.; Taylor, Justin J.; Hobday, Patricia M.; Goudy, Brian D.; Titcombe, Philip J.; Mueller, Daniel L.; Binstadt, Bryce A

doi:10.4049/jimmunol.1201680

Cited by 16 publications

(15 citation statements)

References 45 publications

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“…The development of a preinflammatory condition in the presence of dysregulated excessive adipogenesis is associated with adipose macrophage infiltration and activation. From our study, we can hypothesise a similar process in backfat tissue of FAT pigs, where we identified the overexpression of the gene macrophage scavenger receptor 1 (MSR1), encoding a membrane glycoprotein that in humans is involved in the pathologic deposition of cholesterol in arterial walls during atherogenesis (Haasken et al 2013). Additionally, the overexpression of secreted phosphoprotein 1 (SPP1) in FAT pigs can suggest a hypothesis that this gene encodes a protein acting as a pro-inflammatory cytokine that promotes monocyte chemotaxis and cell motility and might link, in pigs as in mice, fat accumulation to the development of insulin resistance by sustaining inflammation and the accumulation of macrophages in adipose tissue (Nomiyana et al 2007).…”

Section: Genes Involved In Immunity and Inflammation Are More Highly mentioning

confidence: 88%

Transcriptional profiling of subcutaneous adipose tissue in Italian Large White pigs divergent for backfat thickness

Zambonelli¹,

Gaffo

Zappaterra³

et al. 2016

Animal Genetics

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Fat deposition is a widely studied trait in pigs because of its implications with animal growth efficiency, technological and nutritional characteristics of meat products, but the global framework of the biological and molecular processes regulating fat deposition in pigs is still incomplete. This study describes the backfat tissue transcription profile in Italian Large White pigs and reports genes differentially expressed between fat and lean animals according to RNA-seq data. The backfat transcription profile was characterised by the expression of 23 483 genes, of which 54.1% were represented by known genes. Of 63 418 expressed transcripts, about 80% were non-previously annotated isoforms. By comparing the expression level of fat vs. lean pigs, we detected 86 robust differentially expressed transcripts, 72 more highly expressed (e.g. ACP5, BCL2A1, CCR1, CD163, CD1A, EGR2, ENPP1, GPNMB, INHBB, LYZ, MSR1, OLR1, PIK3AP1, PLIN2, SPP1, SLC11A1, STC1) and 14 lower expressed (e.g. ADSSL1, CDO1, DNAJB1, HSPA1A, HSPA1B, HSPA2, HSPB8, IGFBP5, OLFML3) in fat pigs. The main functional categories enriched in differentially expressed genes were immune system process, response to stimulus, cell activation and skeletal system development, for the overexpressed genes, and unfolded protein binding and stress response, for the underexpressed genes, which included five heat shock proteins. Adipose tissue alterations and impaired stress response are linked to inflammation and, in turn, to adipose tissue secretory activity, similar to what is observed in human obesity. Our results provide the opportunity to identify biomarkers of carcass fat traits to improve the pig production chain and to identify genetic factors that regulate the observed differential expression.

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Section: Genes Involved In Immunity and Inflammation Are More Highly mentioning

confidence: 88%

Transcriptional profiling of subcutaneous adipose tissue in Italian Large White pigs divergent for backfat thickness

Zambonelli¹,

Gaffo

Zappaterra³

et al. 2016

Animal Genetics

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“…Besides, MSR1 is a multifunctional receptor expressed primarily on cells of the myeloid lineage [ 47 ]. It positively regulates the activation of macrophages and thus promoting the inflammation [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue

Zheng

2020

IJMS

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Arthritis is the leading cause of disability among adults, while osteoarthritis (OA) is the most common form of arthritis that results in cartilage loss. However, accumulating evidence suggests that the protective hyaline cartilage should not be the sole focus of OA treatment. Particularly, synovium also plays essential roles in OA’s initiation and progression and warrants serious consideration when battling against OA. Thus, biomarkers with similar OA-responsive expressions in cartilage and synovium should be the potential targets for OA treatment. On the other hand, molecules with a distinguished response during OA in cartilage and synovium should be ruled out as OA therapeutic(s) to avoid controversial effects in different tissues. Here, to pave the path for developing a new generation of OA therapeutics, two published transcriptome datasets of knee articular cartilage and synovium were analyzed in-depth. Genes with statistically significantly different expression in OA and healthy cartilage were compared with those in the synovium. Thirty-five genes with similar OA-responsive expression in both tissues were identified while recognizing three genes with opposite OA-responsive alteration trends in cartilage and synovium. These genes were clustered based on the currently available knowledge, and the potential impacts of these clusters in OA were explored.

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“…Several lines of evidence support a role for SR-A in peripheral tolerance [9] , [38] – [42] . For example, it has been reported that SR-A deficiency is protective against diabetic nephropathy in NOD mice [38] , against autoantibody-dependent arthritis and EAE [39] , [40] . Previous reports showed that TNF-α administration in older mice prevented autoimmune diabetes in NOD mice and that TNF-α expression from a young age in TNF-α transgenic NOD mice accelerated diabetes progression [43] – [45] .…”

Section: Discussionmentioning

confidence: 99%

The Dual Role of Scavenger Receptor Class A in Development of Diabetes in Autoimmune NOD Mice

et al. 2014

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Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic β cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A) may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A−/− nonobese diabetic (NOD) mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A−/− NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I∶C)) was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I∶C). In addition, injection of high-dose poly(I∶C) to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A−/− NOD mice compared with untreated SR-A−/− NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A−/− NOD mice treated with poly(I∶C) than in untreated SR-A−/− NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A−/− NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I∶C) treatment even in SR-A−/− NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.

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Macrophage Scavenger Receptor 1 (Msr1, SR-A) Influences B Cell Autoimmunity by Regulating Soluble Autoantigen Concentration

Cited by 16 publications

References 45 publications

Transcriptional profiling of subcutaneous adipose tissue in Italian Large White pigs divergent for backfat thickness

Transcriptional profiling of subcutaneous adipose tissue in Italian Large White pigs divergent for backfat thickness

Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue

The Dual Role of Scavenger Receptor Class A in Development of Diabetes in Autoimmune NOD Mice

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