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J Immunol. 2019 Aug 9. pii: ji1900468. doi: 10.4049/jimmunol.1900468. [Epub ahead of print]

Dendritic Cell Accumulation in the Gut and Central Nervous System Is Differentially Dependent on α4 Integrins.

Author information

1
Abteilung für Experimentelle Neuroimmunologie, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
2
Klinik für Neurologie, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
3
I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
4
Division of Clinical Pathology, Department of Pathology and Immunology, University of Geneva, 1211 Geneva, Switzerland.
5
Center of Allergy and Environment, Helmholtz Center and Technical University of Munich, 80802 Munich, Germany.
6
Institute for Immunology, Biomedical Center, Ludwig Maximilians University of Munich, 82152 Planegg-Martinsried, Germany; and.
7
Abteilung für Experimentelle Neuroimmunologie, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany; thomas.korn@tum.de.
8
Munich Cluster for Systems Neurology, SyNergy, 81377 Munich, Germany.

Abstract

Homing of pathogenic CD4+ T cells to the CNS is dependent on α4 integrins. However, it is uncertain whether α4 integrins are also required for the migration of dendritic cell (DC) subsets, which sample Ags from nonlymphoid tissues to present it to T cells. In this study, after genetic ablation of Itga4 in DCs and monocytes in mice via the promoters of Cd11c and Lyz2 (also known as LysM), respectively, the recruitment of α4 integrin-deficient conventional and plasmacytoid DCs to the CNS was unaffected, whereas α4 integrin-deficient, monocyte-derived DCs accumulated less efficiently in the CNS during experimental autoimmune encephalomyelitis in a competitive setting than their wild-type counterparts. In a noncompetitive setting, α4 integrin deficiency on monocyte-derived DCs was fully compensated. In contrast, in small intestine and colon, the fraction of α4 integrin-deficient CD11b+CD103+ DCs was selectively reduced in steady-state. Yet, T cell-mediated inflammation and host defense against Citrobacter rodentium were not impaired in the absence of α4 integrins on DCs. Thus, inflammatory conditions can promote an environment that is indifferent to α4 integrin expression by DCs.

PMID:
31399516
DOI:
10.4049/jimmunol.1900468

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