| First Author | Moeller J | Year | 2024 |
| Journal | J Endocr Soc | Volume | 8 |
| Issue | 11 | Pages | bvae171 |
| PubMed ID | 39435302 | Mgi Jnum | J:360142 |
| Mgi Id | MGI:7797659 | Doi | 10.1210/jendso/bvae171 |
| Citation | Moeller J, et al. (2024) Ablation of PC1/3 in POMC-Expressing Tissues but Not in Immune Cells Induces Sepsis Hypersensitivity. J Endocr Soc 8(11):bvae171 |
| abstractText | Prohormone convertase 1/3 (PC1/3) is an endopeptidase required for the processing of neuropeptide and endocrine peptide precursors; it is expressed in neuroendocrine tissues as well as in immune cells. In response to endotoxemia, global PC1/3 knockout mice mount a cytokine storm and die rapidly. Further, immune cells isolated from these mice have a pro-inflammatory signature, suggesting that PC1/3 activates an unknown anti-inflammatory peptide precursor in immune cells. Here, we tested this hypothesis using tissue-specific PC1/3 ablation models. Knocking out PC1/3 in the myeloid or the hematopoietic compartment did not induce any phenotype. In contrast, proopiomelanocortin (POMC)-specific PC1/3 knockout mice phenocopied global PC1/3 knockout mice, including an enlarged spleen size and a hyperinflammatory sepsis phenotype in response to mild endotoxemia. This phenotype was prevented by steroid therapy and mimicked by blocking corticoid receptors in wild-type mice. Thus, our data suggest that sepsis hypersensitivity in PC1/3 deficiency is uncoupled from immune cell intrinsic PC1/3 expression and is driven by a lack of anti-inflammatory glucocorticoids due to an impairment in the hypothalamic-pituitary-adrenal axis. |
