Colonic tolerance develops in the iliac lymph nodes and can be established independent of CD103+ dendritic cells

Veenbergen, S. et al. (2016) Colonic tolerance develops in the iliac lymph nodes and can be established independent of CD103+ dendritic cells. Mucosal Immunology, 9(4), pp. 894-906. (doi: 10.1038/mi.2015.118) (PMID:26577569) (PMCID:PMC4871788)

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Abstract

Tolerance to harmless exogenous antigens is the default immune response in the gastrointestinal tract. Although extensive studies have demonstrated the importance of the mesenteric lymph nodes (MLNs) and intestinal CD103+ dendritic cells (DCs) in driving small intestinal tolerance to protein antigen, the structural and immunological basis of colonic tolerance remain poorly understood. We show here that the caudal and iliac lymph nodes (ILNs) are inductive sites for distal colonic immune responses and that colonic T cell-mediated tolerance induction to protein antigen is initiated in these draining lymph nodes and not in MLNs. In agreement, colonic tolerance induction was not altered by mesenteric lymphadenectomy. Despite tolerance development, CD103+CD11b+ DCs, which are the major migratory DC population in the MLNs, and the tolerance-related retinoic acid-generating enzyme RALDH2 were virtually absent from the ILNs. Administration of ovalbumin (OVA) to the distal colon did increase the number of CD11c+MHCIIhi migratory CD103−CD11b+ and CD103+CD11b− DCs in the ILNs. Strikingly, colonic tolerance was intact in Batf3-deficient mice specifically lacking CD103+CD11b− DCs, suggesting that CD103− DCs in the ILNs are sufficient to drive tolerance induction after protein antigen encounter in the distal colon. Altogether, we identify different inductive sites for small intestinal and colonic T-cell responses and reveal that distinct cellular mechanisms are operative to maintain tolerance at these sites.

Item Type:Articles
Additional Information:This work was supported by the Dutch Digestive Foundation grant (WO 10–37) and Sophia Foundation grant 470.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mowat, Professor Allan
Authors: Veenbergen, S., van Berkel, L.A., du Pré, M.F., He, J., Karrich, J.J., Costes, L.M.M., Luk, F., Simons-Oosterhuis, Y., Raatgeep, H.C., Cerovic, V., Cupedo, T., Mowat, A.M., Kelsall, B.L., and Samsom, J.N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Mucosal Immunology
Publisher:Nature Publishing Group
ISSN:1933-0219
ISSN (Online):1935-3456
Published Online:18 November 2015

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