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<p>C-type lectin receptors (CLRs) are a family of pattern recognition receptors that sense diverse microbial and damage-associated molecular patterns. Many CLRs, like Mincle and Dectin-3, are upregulated by TLR4 signaling. In Alcohol-associated Hepatitis (AH), where alcohol consumption leads to leakage of bacterial LPS, TLR4 upregulates CLR expression and increases the diversity of what the immune system can detect, which we call “secondary immune surveillance”. Previously, we found human monocytes upregulate CLRs in response to LPS/TLR4 signaling with much higher expression in AH. In this study, we broaden our understanding of secondary immune surveillance. We find that CLRs are upregulated by many kinds of TLR signaling. Additionally, mouse monocytes and microglia also upregulated CLRs in response to LPS/TLR4 signaling. We used Mincle-KO mice to dissect how loss of one CLR impacts tissue inflammation. Mincle-KO mice were protected from liver inflammation caused by LPS, but experienced worse adipose tissue inflammation, suggesting a shift in the site of injury. Bulk RNA-seq revealed extensive alternative splicing of many CLR genes, with only translatable mRNA detected after LPS. Finally, using bulk RNA-seq data of livers from patients with AH, we observe extensive expression of CLRs, suggesting these receptors may betargets for therapies to reduce inflammation.</p>

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Secondary Immune Surveillance via upregulation of C-type lectin receptors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月1日

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  • Farhin Patel,
  • Emmanuel Boafo,
  • Yurui Zheng,
  • Colin Varnet,
  • Adam Kim

摘要

C-type lectin receptors (CLRs) are a family of pattern recognition receptors that sense diverse microbial and damage-associated molecular patterns. Many CLRs, like Mincle and Dectin-3, are upregulated by TLR4 signaling. In Alcohol-associated Hepatitis (AH), where alcohol consumption leads to leakage of bacterial LPS, TLR4 upregulates CLR expression and increases the diversity of what the immune system can detect, which we call “secondary immune surveillance”. Previously, we found human monocytes upregulate CLRs in response to LPS/TLR4 signaling with much higher expression in AH. In this study, we broaden our understanding of secondary immune surveillance. We find that CLRs are upregulated by many kinds of TLR signaling. Additionally, mouse monocytes and microglia also upregulated CLRs in response to LPS/TLR4 signaling. We used Mincle-KO mice to dissect how loss of one CLR impacts tissue inflammation. Mincle-KO mice were protected from liver inflammation caused by LPS, but experienced worse adipose tissue inflammation, suggesting a shift in the site of injury. Bulk RNA-seq revealed extensive alternative splicing of many CLR genes, with only translatable mRNA detected after LPS. Finally, using bulk RNA-seq data of livers from patients with AH, we observe extensive expression of CLRs, suggesting these receptors may betargets for therapies to reduce inflammation.