Type I interferons inhibition of inflammatory T helper cell responses in systemic lupus erythematosus.

T helper (Th) cells play a central role in systemic lupus erythematosus (SLE). Activated autoreactive Th cells provide the help required for autoreactive B cells to differentiate and produce pathogenic autoAbs. Both autoAb-containing immune complexes and direct effects of inflammatory Th cells promote tissue injury and organ damage.

A macrophage marker, Siglec-1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type I interferons and toll-like receptor agonists.

Objective: Microarray analyses of peripheral blood leukocytes have shown that patients with systemic lupus erythematosus express increased levels of type I interferon (IFN)-regulated genes. In this study we examined gene expression by peripheral blood mononuclear cells (PBMCs) from patients with systemic sclerosis (SSc) to better understand the dysregulation of the immune system in this disease.

Methods: PBMC gene expression was analyzed by microarray and confirmed by real-time polymerase chain reaction (PCR).

Blockade of TLR9 agonist-induced type I interferons promotes inflammatory cytokine IFN-gamma and IL-17 secretion by activated human PBMC.

Type I interferons (IFN) (IFN-alpha/beta) are recognized as both inhibitors and effectors of autoimmune disease. In multiple sclerosis, IFN-beta therapy appears beneficial, in part, due to its suppression of autoimmune inflammatory Th cell responses. In contrast, in systemic lupus erythematosus (SLE) triggering of plasmacytoid DC (pDC) Toll-like receptors (TLRs) by autoimmune complexes (autoICs) results in circulating type I IFN that appear to promote disease by driving autoantigen presentation and autoantibody production.