Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) with unclear etiology and limited treatment options. Immune cell infiltration into the kidneys, a hallmark of LN, triggers tissue damage and proteinuria. CD11b, the α-chain of integrin receptor CD11b/CD18 (also known as αMβ2, Mac-1, and CR3), is highly expressed on the surface of innate immune cells, including macrophages and neutrophils. Genetic variants in the human ITGAM gene, which encodes for CD11b, are strongly associated with susceptibility to SLE, LN, and other complications of SLE. CD11b modulates several key biological functions in innate immune cells, including cell adhesion, migration, and phagocytosis. CD11b also modulates other signaling pathways in these cells, such as the Toll-like receptor signaling pathways, that mediate generation of type I interferons, a key proinflammatory cytokine and circulating biomarker in SLE and LN patients. However, how variants in ITGAM gene contribute to disease pathogenesis has not been completely established. Here, we provide an overview of CD11b modulated mechanisms and the functional consequences of the genetic variants that can drive disease pathogenesis. We also present recent insights from studies after pharmacological activation of CD11b. These studies offer novel mechanisms for development of therapeutics for LN, SLE and other autoimmune diseases.
A systematic review to study the skin complications associated with the bone-anchored hearing aid in relation to surgical techniques. The following databases have been searched: MEDLINE, EMBASE, the Cochrane Library , Google scholar and the PubMed. The literature search date was from January 1977 until November 2013. Randomised controlled trials and retrospective studies were included. Initial search identified 420 publications. Thirty articles met the inclusion criteria of this review. The most common surgical techniques identified were full-thickness skin graft, Dermatome and linear incision techniques. The result shows that dermatome technique is associated with higher rate of skin complications when compared to linear incision and skin graft techniques. Based on the available literature, the use of a linear incision technique appears to be associated with lower skin complications; however, there is limited data available supporting this. Higher quality studies would allow a more reliable comparison between the surgical techniques.
Aqueous humor (AqH) has been shown to have significant immunosuppressive effects on APCs in animal models. We wanted to establish whether, in humans, AqH can regulate dendritic cell (DC) function and to identify the dominant mechanism involved. Human AqH inhibited the capacity of human peripheral blood monocyte-derived DC to induce naive CD4+ T cell proliferation and cytokine production in vitro, associated with a reduction in DC expression of the costimulatory molecule CD86. This was seen both for DC cultured under noninflammatory conditions (immature DC) and for DC stimulated by proinflammatory cytokines (mature DC). DC expression of MHC classes I/II and CD83 was reduced (mature DC only). Myeloid DC from peripheral blood were similarly sensitive to the effects of human AqH, but only under inflammatory conditions. The addition of α-melanocyte stimulating hormone and vasoactive intestinal peptide did not cause significant inhibition at physiological levels. However, the addition of exogenous cortisol at physiological levels recapitulated the AqH-induced reduction in CD86 and inhibition of DC-induced T cell proliferation, and blockade of cortisol in AqH partially reversed its suppressive effects. TGF-β2 had an additional effect with cortisol, and although simultaneous blockade of cortisol and TGF-β2 in AqH reduced its effectiveness, there was still a cortisol- and TGF-β–independent component. In humans, AqH regulates DC maturation and function by the combined actions of cortisol and TGF-β2, a pathway that is likely to contribute to the maintenance of immune privilege in the eye.
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