Dendritic Cell Accumulation in the Gut and Central Nervous System Is Differentially Dependent on α4 Integrins
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Dendritic Cell Accumulation in the Gut and Central Nervous System Is Differentially Dependent on α4 Integrins. / Sie, Christopher; Perez, Laura Garcia; Kreutzfeldt, Mario; Potthast, Maria; Ohnmacht, Caspar; Merkler, Doron; Huber, Samuel; Krug, Anne; Korn, Thomas.
In: J IMMUNOL, Vol. 203, No. 6, 15.09.2019, p. 1417-1427.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -