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SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis

ABSTRACT: SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis

PROVIDER: PRJNA993132 | ENA |

REPOSITORIES: ENA

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SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis [sequencing]

Project description:The innate immune system is finely tuned to enable rapid response to pathogenic stimuli but keep quiescent during tissue homeostasis.Balance of activating and inhibitory signaling sets a threshold for immune activation. Signal regulatory protein (SIRPa) is an immune inhibitory receptor expressed by myeloid cells and interacts with CD47 to inhibit immune cell phagocytosis, migration, and activation. Despite the progress of SIRPa and CD47 antagonist antibodies to promote anti-cancer immunity, it is not yet known whether therapeutic SIRPa receptor agonism could restrain excessive autoimmune inflammation in the context of autoimmunity. Here, we reported that increased neutrophil- and monocyte-associated genes including SIRPA in inflamed tissues biopsies of rheumatoid arthritis and inflammatory bowel diseases, and elevated SIRPA in colonic biopsies is associated with treatment refractory ulcerative colitis patients. We next identified a novel agonistic anti-SIRPa antibody that exhibited potent anti-inflammatory effects in reducing neutrophil and monocytes chemotaxis and tissue infiltration. In preclinical models of arthritis and colitis, anti-SIRPa agonistic antibody ameliorates autoimmune joint inflammation and inflammatory colitis through reducing neutrophils and monocytes in tissues. Our work provides a proof-of-concept for SIRPa receptor agonism for suppressing excessive innate immune activation and autoimmune inflammatory therapeutic treatment

2023-08-24 | GSE235400 | GEO

SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis [array]

Project description:The innate immune system is finely tuned to enable. rapid response to pathogenic stimuli but keep quiescent during tissue homeostasis. Balance of activating and inhibitory signaling sets a threshold for immune activation. Signal regulatory protein (SIRPa) is an immune inhibitory receptor expressed by myeloid cells and interacts with CD47 to inhibit immune cell phagocytosis, migration, and activation. Despite the progress of SIRPa and CD47 antagonist antibodies to promote anti-cancer immunity, it is not yet known whether therapeutic SIRPa receptor agonism could restrain excessive autoimmune inflammation in the context of autoimmunity. Here, we reported that increased neutrophil- and monocyte-associated genes including SIRPA in inflamed tissues biopsies of rheumatoid arthritis and inflammatory bowel diseases, and elevated SIRPA in colonic biopsies is associated with treatment refractory ulcerative colitis patients. We next identified a novel agonistic anti-SIRPa antibody that exhibited potent anti-inflammatory effects in reducing neutrophil and monocytes chemotaxis and tissue infiltration. In preclinical models of arthritis and colitis, anti-SIRPa agonistic antibody ameliorates autoimmune joint inflammation and inflammatory colitis through reducing neutrophils and monocytes in tissues. Our work provides a proof-of-concept for SIRPa receptor agonism for suppressing excessive innate immune activation and autoimmune inflammatory therapeutic treatment

2023-08-24 | GSE236924 | GEO

SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis [array]

Project description:SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis [array]

| PRJNA993141 | ENA

SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis [sequencing]

Project description:SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis [sequencing]

| PRJNA985933 | ENA

SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-24 | GSE236928 | GEO

Bone marrow derived macrophages RNA-Seq (WT vs SIRPa KO)

Project description:RNA transcriptome difference between WT and SIRPa knockout (KO) bone marrow derived macrophages (BMDMs). To understand how SIRPa inhibits the phagocytotic capacity of macrophages, a mouse lacking SIRPa was generated, and the transcriptional profiles of BMDMs from wild-type and SIRPa KO mice were compared, using RNA sequencing.

2023-10-02 | GSE223059 | GEO

Antibody-Mediated Delivery of VEGFC Ameliorates Experimental Chronic Colitis.

Project description:Crohn's disease (CD) and ulcerative colitis (UC) are two distinct forms of inflammatory bowel disease (IBD) characterized by an expanded lymphatic network with impaired functionality both in mouse models and in human patients. In this study, we investigated whether targeted delivery of the pro-lymphangiogenic vascular endothelial growth factor C (VEGFC) to the site of inflammation may represent a new, clinically feasible strategy for treating IBD. To achieve targeting of inflamed tissue, we developed a fusion protein consisting of human VEGFC fused to the F8 antibody (F8-VEGFC), which specifically binds to the extradomain A (EDA) of fibronectin, a spliced isoform almost exclusively expressed in inflamed tissues. The therapeutic activity of intravenously administered F8-VEGFC, compared to a targeted construct lacking VEGFC (F8-SIP), was investigated in a mouse model of dextran sodium sulfate (DSS)-induced colitis. The presence of EDA fibronectin was detected in both human and mouse inflamed colon tissue. Biodistribution studies of radiolabeled F8-VEGFC revealed a specific accumulation of the antibody in the colon of DSS-administered mice, as compared to an untargeted VEGFC fusion protein (KSF-VEGFC) (binding the irrelevant hen egg lysozyme antigen). Systemic treatment with F8-VEGFC significantly reduced the clinical and histological signs of inflammation, expanded the lymphatic vascular network, reduced the density of immune cells, and also decreased the expression of inflammatory cytokines in the inflamed colon. Overall, these results reveal that administration of F8-VEGFC represents a novel and promising approach for the treatment of IBD.

| S-EPMC7088901 | biostudies-literature

Effect of SIRPA perturbation on transcriptome of B16 murine melanoma cells

Project description:To explore the effect of SIRPA perturbation on the expression changes of melanoma differentiation antigens (MDA), which directly mediates the immunogenicity of melanoma cells, we profiled the transcriptomes of B16F10 cells with SIRPA knockdown, overexpression, or control.

2022-08-18 | GSE211226 | GEO

Angelica dahurica Polysaccharides Ameliorates Colitis

Project description:Angelica dahurica Polysaccharides Ameliorates Colitis

| PRJNA1067325 | ENA

Project description:Estrogen-related receptor γ agonist DY131 ameliorates lipopolysaccharide-induced acute liver injury

| PRJNA674766 | ENA