Blocking DCIR mitigates colitis and prevents colorectal tumors by enhancing the GM-CSF-STAT5 pathway
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA787480 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17179836_1.fastq.gz | Fastqsanger.gz | |||
| SRR17179836_2.fastq.gz | Fastqsanger.gz | |||
| SRR17179837_1.fastq.gz | Fastqsanger.gz | |||
| SRR17179837_2.fastq.gz | Fastqsanger.gz | |||
| SRR17179838_1.fastq.gz | Fastqsanger.gz |
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Project description:Dendritic cell immunoreceptor (DCIR; Clec4a2), a member of the C-type lectin receptor family, plays important roles in homeostasis of the immune and bone systems. However, the intestinal role of this molecule is unclear. Here, we show that dextran sodium sulfate (DSS)–induced colitis and azoxymethane-DSS–induced intestinal tumors are reduced in Clec4a2–/– mice independent of intestinal microbiota. STAT5 phosphorylation and expression of Csf2 and tight junction genes are enhanced, while Il17a and Cxcl2 is suppressed in the Clec4a2–/– mouse colon, which exhibits reduced infiltration of neutrophils and myeloid-derived suppressor cells. GM-CSF administration ameliorates DSS colitis associated with reduced Il17a and enhanced tight junction gene expression, whereas anti–GM-CSF exacerbates symptoms. Furthermore, anti-NA2, a ligand for DCIR, ameliorates colitis and prevents colorectal tumors. These observations indicate that blocking DCIR signaling ameliorates colitis and suppresses colonic tumors, suggesting DCIR as a possible target for the treatment of these diseases
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