| First Author | Bülow S | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 3 | Pages | 113929 |
| PubMed ID | 38457343 | Mgi Jnum | J:346703 |
| Mgi Id | MGI:7618043 | Doi | 10.1016/j.celrep.2024.113929 |
| Citation | Bulow S, et al. (2024) Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response. Cell Rep 43(3):113929 |
| abstractText | Neutrophil-derived bactericidal/permeability-increasing protein (BPI) is known for its bactericidal activity against gram-negative bacteria and neutralization of lipopolysaccharide. Here, we define BPI as a potent activator of murine dendritic cells (DCs). As shown in GM-CSF-cultured, bone-marrow-derived cells (BMDCs), BPI induces a distinct stimulation profile including IL-2, IL-6, and tumor necrosis factor expression. Conventional DCs also respond to BPI, while M-CSF-cultivated or peritoneal lavage macrophages do not. Subsequent to BPI stimulation of BMDCs, CD4(+) T cells predominantly secrete IL-22 and, when naive, preferentially differentiate into T helper 22 (Th22) cells. Congruent with the tissue-protective properties of IL-22 and along with impaired IL-22 induction, disease severity is significantly increased during dextran sodium sulfate-induced colitis in BPI-deficient mice. Importantly, physiological diversification of intestinal microbiota fosters BPI-dependent IL-22 induction in CD4(+) T cells derived from mesenteric lymph nodes. In conclusion, BPI is a potent activator of DCs and consecutive Th22 cell differentiation with substantial relevance in intestinal homeostasis. |
