Dendritic Cell Accumulation in the Gut and Central Nervous System Is Differentially Dependent on alpha 4 Integrins

Sie, Christopher; Perez, Laura Garcia; Kreutzfeldt, Mario; Potthast, Maria; Ohnmacht, Caspar; Merkler, Doron; Huber, Samuel; Krug, Anne und Korn, Thomas (2019): Dendritic Cell Accumulation in the Gut and Central Nervous System Is Differentially Dependent on alpha 4 Integrins. In: Journal of Immunology, Bd. 203, Nr. 6: S. 1417-1427

Abstract

Homing of pathogenic CD4(+) T cells to the CNS is dependent on alpha 4 integrins. However, it is uncertain whether alpha 4 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 alpha 4 integrin-deficient conventional and plasmacytoid DCs to the CNS was unaffected, whereas alpha 4 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, alpha 4 integrin deficiency on monocyte-derived DCs was fully compensated. In contrast, in small intestine and colon, the fraction of alpha 4 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 alpha 4 integrins on DCs. Thus, inflammatory conditions can promote an environment that is indifferent to alpha 4 integrin expression by DCs.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0022-1767
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198