The Role of Bone Marrow Stromal Cell Antigen 2 (BST2) in the Migration of Dendritic Cells to Lymph Nodes

Int J Mol Sci. 2024 Dec 27;26(1):149. doi: 10.3390/ijms26010149.

Abstract

Bone marrow stromal antigen 2 (BST2) is a host-restriction factor that plays multiple roles in the antiviral defense of innate immune responses, including the inhibition of viral particle release from virus-infected cells. BST2 may also be involved in the endothelial adhesion and migration of monocytes, but its importance in the immune system is still unclear. Immune cell adhesion and migration are closely related to the initiation of immune responses. In this study, we found that the expressions of the lymph node homing marker chemokine receptor 7 (CCR7) and an adhesion molecule intercellular adhesion molecule 1 (ICAM-1) in conventional dendritic cells (cDCs) were associated with BST2 expression. Interestingly, Bst2-/- cDCs showed lower chemotactic ability, including velocity and accumulative distance toward chemokine ligand 19 (CCL19) gradient in vitro, compared to wild-type cDCs. Bst2-/- cDCs also showed reduced migration and reduced retention capacity in draining lymph nodes in vivo. As a result, Bst2-/- cDCs as antigen-presenting cells induced lower antigen-specific B cell and T cell responses compared to Bst2+/+ cDCs. Notably, mice administered the influenza vaccine via Bst2-/- cDCs exhibited substantially inefficient virus clearance compared to mice administered the Bst2+/+ cDCs vaccine. Therefore, we propose that BST2, which plays a critical role in the effective migration and retention of cDCs, is involved in the development of optimal immunological effects in draining lymph nodes.

Keywords: adhesion molecules; bone marrow stromal antigen 2 (BST2); cell migration; chemokine receptor 7 (CCR7); dendritic cells; intercellular adhesion molecule 1 (ICAM-1).

MeSH terms

  • Animals
  • Antigens, CD* / genetics
  • Antigens, CD* / metabolism
  • Bone Marrow Stromal Antigen 2
  • Cell Movement*
  • Dendritic Cells* / immunology
  • Dendritic Cells* / metabolism
  • GPI-Linked Proteins* / genetics
  • GPI-Linked Proteins* / metabolism
  • Influenza Vaccines / immunology
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymph Nodes* / immunology
  • Lymph Nodes* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • BST2 protein, mouse
  • Antigens, CD
  • GPI-Linked Proteins
  • Influenza Vaccines
  • Receptors, CCR7
  • Intercellular Adhesion Molecule-1
  • Ccr7 protein, mouse
  • Bone Marrow Stromal Antigen 2