Mucosal Langerhans Cells Promote Differentiation of Th17 Cells in a Murine Model of Periodontitis but Are Not Required for Porphyromonas gingivalis–Driven Alveolar Bone Destruction

Abstract

Periodontitis is a chronic oral inflammatory disease affecting one in five individuals that can lead to tooth loss. CD4+ Th cells activated by a microbial biofilm are thought to contribute to the destruction of alveolar bone surrounding teeth by influencing osteoclastogenesis through IL-17A and receptor activator for NF-κB ligand effects. The relative roles of mucosal Ag presentation cells in directing Th cell immune responses against oral pathogens and their contribution to destruction of alveolar bone remain unknown. We tested the contribution of mucosal Langerhans cells (LCs) to alveolar bone homeostasis in mice following oral colonization with a well-characterized human periodontal pathogen, Porphyromonas gingivalis. We found that oral mucosal LCs did not protect from or exacerbate crestal alveolar bone destruction but were responsible for promoting differentiation of Th17 cells specific to P. gingivalis. In mice lacking LCs the Th17 response was suppressed and a Th1 response predominated. Bypassing LCs with systemic immunization of P. gingivalis resulted in a predominantly P. gingivalis–specific Th1 response regardless of whether LCs were present. Interestingly, we find that in vivo clonal expansion of P. gingivalis–specific Th cells and induced regulatory T cells does not depend on mucosal LCs. Furthermore, destruction of crestal alveolar bone induced by P. gingivalis colonization occurred regardless of the presence of mucosal LCs or P. gingivalis–specific Th17 cells. Our data indicate that both LCs and Th17 cells are redundant in contributing to alveolar bone destruction in a murine model of periodontitis.

The therapeutic potential of regulatory T lymphocytes in periodontitis: A systematic review

“…The murine experimental models were used in 100% of the studies, from which the mouse model was the most frequently used animal model (76.2%) . In the studies using mice, 10 studies used the C57BL/6 strain, four studies used the BALB/c strain, and three studies did not specify the animal strain used . In addition, seven studies used only wild‐type mice, nine studies used both wild‐type and knockout mice, and one study used wild‐type, knockout and the 10BiT mice, corresponding to a IL‐10 reporter animal.…”

“…In the studies using mice, 10 studies used the C57BL/6 strain, four studies used the BALB/c strain, and three studies did not specify the animal strain used . In addition, seven studies used only wild‐type mice, nine studies used both wild‐type and knockout mice, and one study used wild‐type, knockout and the 10BiT mice, corresponding to a IL‐10 reporter animal. From them, only eight studies reported the number of mice that were analysed (M = 22.6, SD = 8.30, total = 181 mice).…”

“…Moreover, there was substantial heterogeneity among the protocols to induce experimental periodontitis (Table and ). P. gingivalis was chosen in 57.1% of the studies, including distinct bacterial serotypes, lipopolysaccharide (LPS), heat‐shock proteins (HSP) and fimbriae. On the other hand, Aggregatibacter actinomycetemcomitans strains were used in five studies .…”

“…Distinct animal experimentation protocols were used in the reviewed studies. The murine experimental models were used in 100% of the studies, 3,8,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] from which the mouse model was the most frequently used animal model (76.2%). 3,[12][13][14][15][16][17][18][19][20][21][22][23]25,26,28,30 In the studies using mice, 10 studies used the C57BL/6 strain, 3,12,[14][15][16][17][21][22][23]26 four studies used the BALB/c strain, 13,18,…”

“…3,[12][13][14][15][16][17][18][19][20][21][22][23]25,26,28,30 In the studies using mice, 10 studies used the C57BL/6 strain, 3,12,[14][15][16][17][21][22][23]26 four studies used the BALB/c strain, 13,18,21,25 and three studies did not specify the animal strain used. 19,28,30 In addition, seven studies used only wild-type mice, 12,13,17,18,22,25,26 nine studies used both wild-type and knockout mice, 3,[14][15][16]19,22,23,28,30 and one study used wild-type, knockout and the 10BiT mice, …”