| First Author | Hirano T | Year | 2021 |
| Journal | J Allergy Clin Immunol | Volume | 148 |
| Issue | 2 | Pages | 563-573.e7 |
| PubMed ID | 33581199 | Mgi Jnum | J:343990 |
| Mgi Id | MGI:6764696 | Doi | 10.1016/j.jaci.2020.12.654 |
| Citation | Hirano T, et al. (2021) PD-L1 on mast cells suppresses effector CD8(+) T-cell activation in the skin in murine contact hypersensitivity. J Allergy Clin Immunol 148(2):563-573.e7 |
| abstractText | BACKGROUND: The programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is known to inhibit the activation of effector CD8(+) T cells. However, just how this regulatory pathway is involved in the pathophysiology of CD8(+) T-cell-mediated inflammatory skin diseases remains unclear. OBJECTIVE: Our aim was to elucidate the mechanisms by which the PD-1/PD-L1 pathway exerts its regulatory roles in CD8(+) T-cell-mediated cutaneous immune responses. METHODS: PD-L1-deficient (Pdl1(-/-)) mice were used for the murine contact hypersensitivity model. Inflammatory responses such as IFN-gamma production from CD8(+) T cells in the skin was evaluated by flow cytometry. RESULTS: Compared with wild-type mice, Pdl1(-/-) mice exhibited exacerbated ear swelling and increased numbers of IFN-gamma(+) CD8(+) T cells in the skin. Adoptive T-cell transfer experiments revealed the involvement of the PD-1/PD-L1 pathway in the elicitation phase of contact hypersensitivity. Bone marrow chimera experiments showed that PD-L1 on radioresistant cells was responsible for this regulatory pathway. Flow cytometric analysis revealed that among the radioresistant cells in the skin, PD-L1 was most highly expressed on mast cells (MCs) before and after elicitation. Administration of anti-PD-L1 blocking antibody during the elicitation phase significantly enhanced ear swelling responses and increased the number of IFN-gamma(+)CD8(+) T cells in the skin of wild-type mice, whereas no significant effects were observed in MC-deficient (WBB6F1/J-Kit(W)/Kit(W-v)/J and C57BL/6-KitW(-sh)/W(-sh)) mice. The high level of expression of PD-L1 on human skin MCs was confirmed by database analysis and immunohistochemical analysis. CONCLUSION: PD-L1 on MCs negatively regulates CD8(+) T-cell activation in the skin. |
