Blood dendritic cells and DC-poietins in systemic lupus erythematosus.
Dendritic cells (DCs) control immunity and tolerance. Hence, we surmised that systemic lupus erythematosus (SLE), a systemic autoimmune disease with autoreactive T and B cells, might be due to alterations in DC homeostasis. Taken together, our results demonstrate profound alterations of DCs and DC-poietins homeostasis in SLE. Elevated levels of interferon-alpha (IFN) in serum of SLE patients coexist with decreased numbers of cells producing IFN-alpha, i.e., plasmacytoid dendritic cells (PDCs). Decreased numbers of circulating DCs correlate with increased levels of soluble tumor necrosis factor (TNF) receptors, thus suggesting the potential role of TNF pathway in the observed DC alterations. Finally, increased FMS-like tyrosine kinase 3-ligand (FLT3-L) and its correlation with soluble TNF receptors suggest a physiologic response to compensate low DC numbers. Although IFN-alpha remains at the center of immunologic aberrations in SLE, it remains to be determined whether increased shedding of soluble TNF receptors could also be ascribed to IFN-alpha.
Gill
Michelle A
MA
Baylor Institute for Immunology Research, Dallas, Texas, USA.
Blanco
Patrick
P
Arce
Edsel
E
Pascual
Virginia
V
Banchereau
Jacques
J
Palucka
A Karolina
AK
D000293:Adolescent; D002648:Child; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*
D016898:Interferon-alpha; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein