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Defective migration of monocyte‐derived dendritic cells in LAD‐1 immunodeficiency
Author(s) -
Fiorini Maurilia,
Vermi William,
Facchetti Fabio,
Moratto Daniele,
Alessandri Giulio,
Notarangelo Lucia,
Caruso Arnaldo,
Grigolato Piergiovanni,
Ugazio Alberto G.,
Notarangelo Luigi D.,
Badolato Raffaele
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.4.650
Subject(s) - biology , cd18 , monocyte , immunology , integrin , dendritic cell , ccl19 , leukocyte adhesion deficiency , follicular dendritic cells , chemokine , tumor necrosis factor alpha , microbiology and biotechnology , pathology , immune system , chemokine receptor , integrin alpha m , t cell , receptor , medicine , antigen presenting cell , biochemistry
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‐3β, 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.