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

J Immunol. 2019 Sep 15;203(6):1417-1427. doi: 10.4049/jimmunol.1900468. Epub 2019 Aug 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • CD11b Antigen / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cell Line, Tumor
  • Central Nervous System / immunology*
  • Citrobacter rodentium / immunology
  • Colon / immunology*
  • Dendritic Cells / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Inflammation / immunology
  • Integrin alpha Chains / immunology
  • Integrin alpha4 / immunology*
  • Intestine, Small / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / immunology


  • Antigens, CD
  • CD11b Antigen
  • Integrin alpha Chains
  • alpha E integrins
  • Integrin alpha4