Research Highlight | Inflammation | 2026
A recent study from Professor Hebin Liu’s team at Soochow University, published in Inflammation, identified a new regulatory pathway linking the immune adaptor protein ADAP to SPI1 and S100A8/A9 signaling in macrophages during colitis.
ADAP Regulates SPI1 Protein Stability to Control Inflammation
Using a DSS-induced acute colitis model, ADAP-deficient mice, transcriptomic and single-cell analyses, the researchers investigated how ADAP regulates intestinal inflammation.
The study revealed that ADAP promotes the activity of the E3 ubiquitin ligase FBXW7, which facilitates K48-linked ubiquitination and proteasomal degradation of SPI1. Loss of ADAP leads to SPI1 accumulation, increased binding to the S100A8/A9 promoters, and enhanced S100A8/A9 transcription, contributing to stronger inflammatory signaling and aggravated colitis.
Importantly, SPI1 mRNA levels remained unchanged while SPI1 protein increased, supporting a post-translational mechanism regulating SPI1 stability.
Macrophage depletion with clodronate liposomes further reversed the aggravated inflammatory phenotype in ADAP-deficient mice, highlighting macrophages as key effector cells in this pathway.
Figure 1. ADAP-mediated inhibition of SPI1 regulates the S100A8/A9 signaling pathway in macrophages, thereby modulating the development and progression of colitis.
Multi-Level Mechanistic Validation
The researchers combined multiple approaches to establish the ADAP–FBXW7–SPI1–S100A8/A9 axis:
- DSS-induced colitis for in vivo disease modeling
- RNA-seq and single-cell analysis for pathway and cell-type profiling
- RT-qPCR for gene expression analysis
- CUT&RUN to examine SPI1 binding to target promoters
- Dual-luciferase reporter assays to validate transcriptional regulation
- Ubiquitination analysis to investigate SPI1 protein stability
Together, these approaches connected disease phenotypes with transcriptional and post-translational mechanisms.
Yeasen Products Supporting the Study
Several Yeasen products supported key experimental steps in this research:
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Product |
Cat# |
Application |
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60316ES |
DSS-induced acute colitis model |
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|
40337ES |
In vivo macrophage depletion |
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Hifair™ II 1st Strand cDNA Synthesis Kit |
11119ES |
RNA reverse transcription |
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11184ES |
Gene expression analysis |
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11402ES |
Promoter activity analysis |
Reference:
Inhibition of SPI1 by ADAP Regulates S100A8/A9 Signaling in Macrophages to Control the Development of Colitis
Inflammation, 2026. DOI: 10.1007/s10753-025-02363-9