| First Author | Kaur K | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 13 | Pages | 110178 |
| PubMed ID | 34965421 | Mgi Jnum | J:328272 |
| Mgi Id | MGI:6881845 | Doi | 10.1016/j.celrep.2021.110178 |
| Citation | Kaur K, et al. (2021) GM-CSF production by non-classical monocytes controls antagonistic LPS-driven functions in allergic inflammation. Cell Rep 37(13):110178 |
| abstractText | Lipopolysaccharide (LPS) can either promote or prevent T helper 2 (Th2) cell allergic responses. However, the underlying mechanism remains unknown. We show here that LPS activity switches from pro-pathogenic to protective depending on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by non-classical monocytes. In the absence of GM-CSF, LPS can favor pathogenic Th2 cell responses by supporting the trafficking of lung-migratory dendritic cells (mDC2s) into the lung-draining lymph node. However, when non-classical monocytes produce GM-CSF, LPS and GM-CSF synergize to differentiate monocyte-derived DCs from classical Ly6C(hi) monocytes that instruct mDC2s for Th2 cell suppression. Importantly, only allergens with cysteine protease activity trigger GM-CSF production by non-classical monocytes. Hence, the therapeutic effect of LPS is restricted to allergens with this enzymatic activity. Treatment with GM-CSF, however, restores the protective effects of LPS. Thus, GM-CSF produced by non-classical monocytes acts as a rheostat that fine-tunes the pathogenic and therapeutic functions of LPS. |
