Major Histocompatibility Complex II Expression on Oral Langerhans Cells Differentially Regulates Mucosal CD4 and CD8 T Cells

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Abstract

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 (LCΔMHC-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 LCΔMHC-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 LCΔMHC-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.

Original languageEnglish (US)
Pages (from-to)573-584.e1
JournalJournal of Investigative Dermatology
Volume144
Issue number3
DOIs
StatePublished - Mar 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

  • CD4 T cells
  • CD8 T cells
  • Langerhans cells
  • Oral mucosa
  • T helper 17 (Th17)

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