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

TY - JOUR

T1 - Dendritic Cell Accumulation in the Gut and Central Nervous System Is Differentially Dependent on α4 Integrins

AU - Sie, Christopher

AU - Perez, Laura Garcia

AU - Kreutzfeldt, Mario

AU - Potthast, Maria

AU - Ohnmacht, Caspar

AU - Merkler, Doron

AU - Huber, Samuel

AU - Krug, Anne

AU - Korn, Thomas

N1 - Copyright © 2019 by The American Association of Immunologists, Inc.

PY - 2019/9/15

Y1 - 2019/9/15

N2 - 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.

AB - 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.

U2 - 10.4049/jimmunol.1900468

DO - 10.4049/jimmunol.1900468

M3 - SCORING: Journal article

C2 - 31399516

VL - 203

SP - 1417

EP - 1427

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 6

ER -