Cholera Toxin Promotes Th17 Cell Differentiation by Modulating Expression of Polarizing Cytokines and the Antigen-Presenting Potential of Dendritic Cells.
Cholera toxin (CT), an exotoxin produced by Vibrio cholera, acts as a mucosal adjuvant. In a previous study, we showed that CT skews differentiation of CD4 T cells to IL-17-producing Th17 cells. Here, we found that intranasal administration of CT induced migration of migratory dendritic cell (DC) populations, CD103+ DCs and CD11bhi DCs, to the lung draining mediastinal lymph nodes (medLN). Among those DC subsets, CD11bhi DCs that were relatively immature had a major role in Th17 cell differentiation after administration of CT. CT-treated BMDCs showed reduced expression of MHC class II and CD86, similar to CD11bhi DCs in medLN, and these BMDCs promoted Th17 cell differentiation more potently than other BMDCs expressing higher levels of MHC class II and CD86. By analyzing the expression of activation markers such as CD25 and CD69, proliferation and IL-2 production, we determined that CT-treated BMDCs showed diminished antigen-presenting potential to CD4+ T cells compared with normal BMDCs. We also found that CT-stimulated BMDCs promote activin A expression as well as IL-6 and IL-1β, and activin A had a synergic role with TGF-β1 in CT-mediated Th17 cell differentiation. Taken together, our results suggest that CT-stimulated DCs promote Th17 cell differentiation by not only modulating antigen-presenting potential but also inducing Th polarizing cytokines.
Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
Jung-Ok
JO
Kang
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Kyunggi-Do, Korea.
Jee-Boong
JB
Lee
Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
Jun
http://orcid.org/0000-0002-8423-5987
J
Chang
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D016764:Cell Polarity / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002772:Cholera Toxin / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058504:Th17 Cells / Q000187:drug effects* / Q000502:physiology
D016207:Cytokines; D002772:Cholera Toxin