| First Author | Fischer LA | Year | 2024 |
| Journal | J Invest Dermatol | Volume | 144 |
| Issue | 3 | Pages | 573-584.e1 |
| PubMed ID | 37838330 | Mgi Jnum | J:349144 |
| Mgi Id | MGI:7646019 | Doi | 10.1016/j.jid.2023.09.277 |
| Citation | Fischer LA, et al. (2024) Major Histocompatibility Complex II Expression on Oral Langerhans Cells Differentially Regulates Mucosal CD4 and CD8 T Cells. J Invest Dermatol 144(3):573-584.e1 |
| abstractText | In murine periodontitis, the T helper (Th)17 response against Porphyromonas gingivalis in cervical lymph node is abrogated by diphtheria toxin-driven depletion of Langerhans cells (LCs). We determined the impact of major histocompatibility complex class II (MHC-II) presentation in LCs on Th17 cells in the oral mucosa of mice. Using an established human-Langerin promoter-Cre mouse model, we generated LC-specific deletion of the H2-Ab1 (MHC-II) gene. MHC-II expression was ablated in 81.2% of oral-resident LCs compared with >99% of skin-resident LCs. MHC-II (LC(DeltaMHC-II)) depletion did not reduce the number of CD4 T cells nor the frequency of Th17 cells compared with that in wild-type mice. However, the frequencies of Th1 cells decreased, and Helios(+) T-regulatory cells increased. In ligature-induced periodontitis, the numbers of CD4 T cells and Th17 cells were similar in LC(DeltaMHC-II) and wild-type mice. Normal numbers of Th17 cells can therefore be sustained by as little as 18.8% of MHC-II-expressing LCs in oral mucosa. Unexpectedly, oral mucosa CD8 T cells increased >25-fold in LC(DeltaMHC-II) mice. Hence, these residual MHC-II-expressing LCs appear unable to suppress the local expansion of CD8 T cells while sufficient to sustain a homeostatic CD4 T-cell response. Reducing the expression of MHC-II on specific LC subpopulations may ultimately boost CD8-mediated intraepithelial surveillance at mucosal surfaces. |
