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

First Author  Sie C Year  2019
Journal  J Immunol Volume  203
Issue  6 Pages  1417-1427
PubMed ID  31399516 Mgi Jnum  J:279245
Mgi Id  MGI:6360375 Doi  10.4049/jimmunol.1900468
Citation  Sie C, et al. (2019) Dendritic Cell Accumulation in the Gut and Central Nervous System Is Differentially Dependent on alpha4 Integrins. J Immunol 203(6):1417-1427
abstractText  Homing of pathogenic CD4(+) T cells to the CNS is dependent on alpha4 integrins. However, it is uncertain whether alpha4 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 alpha4 integrin-deficient conventional and plasmacytoid DCs to the CNS was unaffected, whereas alpha4 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, alpha4 integrin deficiency on monocyte-derived DCs was fully compensated. In contrast, in small intestine and colon, the fraction of alpha4 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 alpha4 integrins on DCs. Thus, inflammatory conditions can promote an environment that is indifferent to alpha4 integrin expression by DCs.
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