In Brief

Development

Langerhans cells arise from monocytes in vivo. Ginhoux, F. et al. Nature Immunol. 29 Jan 2006 (doi:10.1038/ni1307)

Despite numerous attempts, the circulating precursors that give rise to skin-resident dendritic cells, known as Langerhans cells (LCs), have not been unequivocally defined. Using fluorescent latex beads, the authors tracked the fate of individual precursor populations in mice subjected to skin injury, which eliminates LCs and induces repopulation by circulating precursors. Monocytes that express high levels of Gr1 homed to inflamed skin and proliferated in situ before differentiating into LCs in 2–3 weeks, indicating that Gr1^hi monocytes are direct precursors of LCs. The receptor for colony-stimulating factor 1 (CSF1R) was shown to be crucial for this process, as CSF1R-deficient bone-marrow progenitors failed to reconstitute the LC pool after skin injury.

Autoimmunity

Blocking the α4 integrin–paxillin interaction selectively impairs mononuclear leukocyte recruitment to an inflammatory site. Féral, C. C. et al. J. Clin. Invest. 9 Feb 2006 (doi:10.1172/JCI26091)

Reagents that block the interaction between α₄-integrin and VCAM1 (vascular cell-adhesion molecule 1) have been used to treat human autoimmune diseases, such as multiple sclerosis, because of their ability to inhibit the recruitment of lymphocytes to sites of inflammation. However, this therapy can cause adverse side effects, such as impaired immunity and haematopoiesis. To avoid this, the authors generated mice with a mutation in α₄-integrin that blocks its ability to bind the signalling adaptor protein paxillin. This specifically inhibited the migration of lymphocytes and monocytes to the peritoneum in response to thioglycollate-induced inflammation, but it did not affect their homing to lymph nodes, the generation of humoral immune responses or haematopoiesis, which were all normal in the α₄-integrin-mutant mice. So, pharmaceutical targeting of the α₄-integrin–paxillin interaction might be important for future treatments of inflammatory disease.

T cells

Complement-induced regulatory T cells suppress T-cell responses but allow for dendritic-cell maturation. Barchet, W. et al. Blood 107, 1497–1504 (2006)

Activation of T cells through the T-cell receptor and CD46 — a complement regulator — induces T cells with a regulatory phenotype that produce high levels of interleukin-10 (IL-10) and suppress the activation of bystander T cells. Barchet et al. examined the effect of these CD46-induced regulatory-like T cells on dendritic cells (DCs) and found that the maturation of DCs was not suppressed. In addition to producing high levels of IL-10, these T cells secrete granulocyte/macrophage colony-stimulating factor (GM-CSF) and soluble CD40 ligand, which were shown to function as a growth factor and to reverse the inhibitory effects of IL-10 on DCs, respectively. Therefore, through a distinct cytokine profile, these complement-induced regulatory-like T cells allow DC maturation but inhibit T-cell responses.