| First Author | Uto T | Year | 2018 |
| Journal | J Allergy Clin Immunol | Volume | 141 |
| Issue | 6 | Pages | 2156-2167.e9 |
| PubMed ID | 29477579 | Mgi Jnum | J:347613 |
| Mgi Id | MGI:7625741 | Doi | 10.1016/j.jaci.2017.11.048 |
| Citation | Uto T, et al. (2018) Critical role of plasmacytoid dendritic cells in induction of oral tolerance. J Allergy Clin Immunol 141(6):2156-2167.e9 |
| abstractText | BACKGROUND: Exposure to dietary constituents through the mucosal surface of the gastrointestinal tract generates oral tolerance that prevents deleterious T cell-mediated immunity. Although oral tolerance is an active process that involves emergence of CD4(+) forkhead box p3 (Foxp3)(+) regulatory T (Treg) cells in gut-associated lymphoid tissues (GALTs) for suppression of effector T (Teff) cells, how antigen-presenting cells initiate this process remains unclear. OBJECTIVE: We sought to determine the role of plasmacytoid dendritic cells (pDCs), which are known as unconventional antigen-presenting cells, in establishment of oral tolerance. METHODS: GALT-associated pDCs in wild-type mice were examined for their ability to induce differentiation of CD4(+) Teff cells and CD4(+)Foxp3(+) Treg cells in vitro. Wild-type and pDC-ablated mice were fed oral antigen to compare their intestinal generation of CD4(+)Foxp3(+) Treg cells and induction of oral tolerance to protect against Teff cell-mediated allergic inflammation. RESULTS: GALT-associated pDCs preferentially generate CD4(+)Foxp3(+) Treg cells rather than CD4(+) Teff cells, and such generation requires an autocrine loop of TGF-beta for its robust production. A deficiency of pDCs abrogates antigen-specific de novo generation of CD4(+)Foxp3(+) Treg cells occurring in GALT after antigenic feeding. Furthermore, the absence of pDCs impairs development of oral tolerance, which ameliorates the progression of delayed-type hypersensitivity and systemic anaphylaxis, as well as allergic asthma, accompanied by an enhanced antigen-specific CD4(+) Teff cell response and antibody production. CONCLUSION: pDCs are required for establishing oral tolerance to prevent undesirable allergic responses, and they might serve a key role in maintaining gastrointestinal immune homeostasis. |
