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

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

SUBMITTER: Sie C 

PROVIDER: S-EPMC6731453 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature