Sensing Tissue Damage by Myeloid C-Type Lectin Receptors

Transcriptional profiling of macrophages in situ in metastatic melanoma reveals localization-dependent phenotypes and function

“… 55 DEC-205 can also be expressed in macrophages in certain tissue conditions and localization. 56 , 57 Our findings on the positive correlation between expression of LY75 in melanoma and patient survival are in line with a recent study 58 showing that LY75 expression in whole tumor samples from TCGA datasets significantly correlated with good patient survival and, using computational approaches, demonstrating a correlation between LY75 expression, and NK cell infiltration and activation in melanoma. Herein, we show LY75 expression predominantly in the tumor stroma and it is possible that both NK cells as well as DCs contribute to this.…”

Myeloid cells in sensing of tissue damage

“…The negative regulation of neutrophil infiltration under sterile tissue damage conditions was also described for another myeloid CLR, CLEC12A/CLL-1 [ 1 ]. In this case, monosodium urate (MSU) crystals are the recognized DAMPs.…”

“…Although the triggering of some immunogenic cell death programs such as necroptosis or pyroptosis is well regulated at the molecular level [ 1 ], the eventual consequence of this death processes is the disruption of the cell integrity and the release of a massive ‘cocktail’ of intracellular matter. In this scenario, it is expected that a mix of DAMPs, rather than a single one, drive immunogenic responses.…”

“…Because of this damage, tissue homeostasis is altered, impacting on its performance. At the cellular level, the injury can trigger Accidental Cell Death (ACD) such as necrosis or Regulated Cell Death (RCD) mechanisms such as pyroptosis or necroptosis [ 1 , 2 ]. In any case, the ultimate consequence of all these phenomena is cell death and the exposure and release of intracellular content to the extracellular environment.…”

Neuroinflammation of microglia polarization in intracerebral hemorrhage and its potential targets for intervention

“…CLRs’ dysregulation results in the production of inflammatory mediators and the development of inflammatory diseases following excessive injury. Microglial macrophage-inducible C-type lectin (Mincle), a critical member in CLRs, widely expressed on antigen-presenting cells (APCs), including macrophages, binds nuclear spliceosome-Associated Protein 130 (SAP130) from necrotic cells to enhance neuroinflammation (Del Fresno et al, 2020 ; He et al, 2022 ). After the injury, Mincle and its activated downstream spleen tyrosine kinase (Syk) boost inflammatory gene expression levels in alcohol-induced liver injury mice (Kim et al, 2018 ).…”