Migratory CD103+ dendritic cells suppress helminth-driven type 2 immunity through constitutive expression of IL-12

Everts, B. and Tussiwand, R. and Dreesen, L. and Fairfax, K. C. and Huang, S. C. and Smith, A. M. and O'Neill, C. M. and Lam, W. Y. and Edelson, B. T. and Urban, J.F. and Murphy, K. M. and Pearce, E. J.. (2016) Migratory CD103+ dendritic cells suppress helminth-driven type 2 immunity through constitutive expression of IL-12. J Exp Med, 213 (1). pp. 35-51.

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CD8alpha(+) and CD103(+) dendritic cells (DCs) play a central role in the development of type 1 immune responses. However, their role in type 2 immunity remains unclear. We examined this issue using Batf3(-/-) mice, in which both of these DC subsets are missing. We found that Th2 cell responses, and related events such as eosinophilia, alternative macrophage activation, and immunoglobulin class switching to IgG1, were enhanced in Batf3(-/-) mice responding to helminth parasites. This had beneficial or detrimental consequences depending on the context. For example, Batf3 deficiency converted a normally chronic intestinal infection with Heligmosomoides polygyrus into an infection that was rapidly controlled. However, liver fibrosis, an IL-13-mediated pathological consequence of wound healing in chronic schistosomiasis, was exacerbated in Batf3(-/-) mice infected with Schistosoma mansoni. Mechanistically, steady-state production of IL-12 by migratory CD103(+) DCs, independent of signals from commensals or TLR-initiated events, was necessary and sufficient to exert the suppressive effects on Th2 response development. These findings identify a previously unrecognized role for migratory CD103(+) DCs in antagonizing type 2 immune responses.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immune Regulation (Tussiwand)
UniBasel Contributors:Tussiwand, Roxane
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1540-9538 (Electronic)0022-1007 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 May 2020 07:53
Deposited On:25 May 2020 07:53

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