CD38 orchestrates migration, survival, and Th1 immune response

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IMMUNOBIOLOGY

CD38 orchestrates migration, survival, and Th1 immune response of

human mature dendritic cells

Loredana Frasca, Giorgio Fedele, Silvia Deaglio, Cristina Capuano,

Raffaella Palazzo, Tiziana Vaisitti, Fabio Malavasi, and Clara

Ausiello

From the Department of Infectious, Parasitic, and Immune-mediated

Diseases, Istituto Superiore di Sanità, Rome; and the Department of

Genetics, Biology, and Biochemistry, University of Turin Medical

School, Italy.

CD38, an ectoenzyme and a signaling receptor, is a novel marker of

human mature monocyte-derived dendritic cells (MDDCs). The working

hypothesis is that CD38 is not only a marker but also contributes to

functions specifically gained by MDDCs with maturation. This was

tested by assessing the role(s) of CD38 after signaling with

agonistic anti-CD38 monoclonal antibodies or by blocking the

interactions taking place between CD38 and CD31, its counterreceptor.

The results indicate the following: (1) CD38 engagement in MDDCs

ensures efficient chemotaxis and transendothelial migration driven by

CC chemokine ligand 21 (CCL21); (2) CD38 is laterally associated with

the CCL21-specific CC chemokine receptor 7 and with CD83 and CD11b;

(3) CD38 localizes in membrane lipid domains; (4) CD38 signaling

contributes to support longevity of lipopolysaccharide (LPS)–matured

MDDCs after growth factor withdrawal; and (5) IFN- is produced by

cocultured T lymphocytes, thus affecting T-helper 1 (Th1)

polarization. These data suggest that the localization of CD38 in

lipid rafts and its multiple interactions with signaling receptors

rule innate and adaptive immune responses by tuning DC migration,

survival, and Th1-polarization ability. These findings may lay out

the basis to assess the functional role(s) of human CD38 in

infections, autoimmune diseases, and neoplastic disorders.