ADAP–SPI1–S100A8/A9 Axis Reveals a New Regulatory Mechanism in Colitis

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.
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:

Product

Cat#

Application

DSS (Dextran Sulfate Sodium)

60316ES

DSS-induced acute colitis model

Clodronate Liposomes

40337ES

In vivo macrophage depletion

Hifair™ II 1st Strand cDNA Synthesis Kit

11119ES

RNA reverse transcription

Hieff UNICON™ Universal Blue qPCR SYBR Green Master Mix

11184ES

Gene expression analysis

Dual-Luciferase Reporter Gene Assay Kit

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

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