Allograft inflammatory factor-1 and its immune regulation

Abstract

The allograft inflammatory factor-1 (AIF-1) is a 17 kDa interferon-gamma (IFN-gamma) inducible Ca(2+)-binding EF-hand protein that is encoded within the HLA class III genomic region. Three proteins including ionized Ca(2+)-binding adaptor 1, microglia response factor-1, and daintain are identical with AIF-1. The expression of AIF-1 was mostly limited to the monocyte/macrophage lineage, and augmented by cytokines such as IFN-gamma. It was assumed that AIF-1 was a novel molecule involved in inflammatory responses, allograft rejection, as well as the activation and function of macrophages. However, it has been reported that AIF-1 is also expressed in macrophages and microglial cells in autoimmune diseases such as experimental autoimmune encephalomyelitis, neuritis and uveitis models, suggesting that AIF-1 may play a pivotal role in autoimmunity. In the present manuscript, the genomic and functional characteristics of AIF-1 family proteins as well as their immune regulatory effects are reviewed.

Genetic variants of the HLA-A, HLA-B and AIF1 loci show independent associations with type 1 diabetes in Norwegian families

“…The AIF1 protein is involved in inflammatory responses, allograft rejection and macrophage regulation, 41 and has been implicated in T1D by functional studies, showing regulatory effects on insulin secretion in mice and accumulation in the pancreas of prediabetic Bio-Breeding (BB) rats. 42 Also, a number of studies have implicated this protein in other AIDs, 41 including a recent report showing that AIF1 may be crucial in the pathogenesis of rheumatoid arthritis.…”

“…The AIF1 protein is involved in inflammatory responses, allograft rejection and macrophage regulation, 41 and has been implicated in T1D by functional studies, showing regulatory effects on insulin secretion in mice and accumulation in the pancreas of prediabetic Bio-Breeding (BB) rats. 42 Also, a number of studies have implicated this protein in other AIDs, 41 including a recent report showing that AIF1 may be crucial in the pathogenesis of rheumatoid arthritis. 43 In addition to rs2259571, we observed an independent association of rs3132451 in the promoter of the same gene, but this result was most likely an artifact, both judging from the heterogeneity within each of the two individual DRB1-DQA1-DQB1 haplotypes the associations mapped to and the negative result in the T1DGC families.…”

Allograft Inflammatory Factor-1 is Up-regulated in Warm and Cold Ischemia-Reperfusion Injury in Rat Liver and May be Inhibited by FK506

“…In the present study, immunohistochemistry revealed that sinusoidal regions, but not hepatic cell regions, were the main source of AIF-1 in IR liver injury. Previous studies have indicated that inflammatory cytokines, such as IFN-g, IL-1b, and transforming growth factor (TGF)-b, are the most potent inducers of AIF-1 expression [3,[22][23][24]. Indeed, we discovered that AIF-1 levels paralleled IFN-g levels in rats after reperfusion, and in rat macrophages after stimulation with IFN-g and IL-1b, the expression of AIF-1 was up-regulated.…”

Differential gene expression in chronic inflammatory demyelinating polyneuropathy (CIDP) skin biopsies

“…AIF-1 is produced by activated macrophages in transplant rejection and autoimmune disorders [16,17], and LYVE-1 is a marker for lymphatic endothelium which is also expressed by activated bone marrow and tissue macrophages [18]. FYB, also called ADAP (Adhesion and Degranulation Promoting Adaptor Protein), mediates signaling from T-cell antigen receptors to integrins, leading to enhanced cellular adhesion [19].…”