Defective migration of monocyte-derived dendritic cells in LAD-1 immunodeficiency

Maurilia Fiorini, William Vermi, Fabio Facchetti, Daniele Moratto, Giulio Alessandri, Lucia Notarangelo, Arnaldo Caruso, Piergiovanni Grigolato, Alberto G. Ugazio, Luigi D. Notarangelo, Raffaele Badolato

Research output: Contribution to journalArticlepeer-review

Abstract

β2 Integrins (CD18) are required for leukocyte migration. In fact, the absence of CD18 results in type-1 leukocyte adhesion deficiency (LAD-1). We analyzed the distribution phenotype and function of dendritic cells (DCs) in three LAD-1 patients with homozygous mutations of CD18. Two of them did not express CD18 (Patients A and C), and the other subject (Patient B) displayed reduced expression of β2 integrins because of a missense mutation. Analysis of DCs derived from Patients A and B showed an abnormal morphology and a severe impairment in transendothelial migration and chemotactic response to CCL19/macrophage inflammatory protein-β3, suggesting that CD18 is required for migration of monocyte-derived DCs. Nevertheless, DCs displayed normal macropinocytosis and underwent normal maturation after addition of tumor necrosis factor α. Finally, immunohistochemical analysis of lymph nodes from subjects B and C revealed a significant reduction in the number of factor-XIIIa+ interstitial DCs in the interfollicular area in both patients, suggesting that CD18 plays a role in the migration of these cells in vivo.

Original languageEnglish
Pages (from-to)650-656
Number of pages7
JournalJournal of Leukocyte Biology
Volume72
Issue number4
Publication statusPublished - Oct 1 2002

Keywords

  • Adhesion molecules
  • Cell trafficking
  • Human
  • Immunodeficiency diseases

ASJC Scopus subject areas

  • Cell Biology

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