ASCs induce a distinct regulatory activation state of macrophages which possess potent immunomodulatory ability and therapeutic potential in inflammatory bowel diseases and sepsis.
Objective. Rheumatoid arthritis (RA) is an autoimmune disease caused by loss of immunologic self tolerance and characterized by chronic joint inflammation. Cells isolated from human amniotic membrane (HAMCs) were recently found to display immunosuppressive properties. The aim of this study was to characterize the effect of HAMCs on antigen-specific T cell responses in RA patients and to evaluate their therapeutic potential in a preclinical experimental model of RA.Methods. We investigated the effects of HAMCs on collagen-reactive T cell proliferation and cytokine production, on the production of mediators
Cortistatin is a cyclic-neuropeptide produced by brain cortex and immune cells that shows potent anti-inflammatory activity. In this article, we investigated the effect of cortistatin in two models of experimental autoimmune encephalomyelitis (EAE) that mirror chronic and relapsing-remitting multiple sclerosis. A short-term systemic treatment with cortistatin reduced clinical severity and incidence of EAE, the appearance of inflammatory infiltrates in spinal cord, and the subsequent demyelination and axonal damage. This effect was associated with a reduction of the two deleterious components of the disease, namely, the autoimmune and inflammatory response. Cortistatin decreased the presence/activation of encephalitogenic Th1 and Th17 cells in periphery and nervous system, and downregulated various inflammatory mediators, whereas it increased the number of regulatory T cells with suppressive effects on the encephalitogenic response. Moreover, cortistatin regulated glial activity and favored an active program of neuroprotection/regeneration. We further used cortistatin-deficient mice to investigate the role of endogenous cortistatin in the control of immune responses. Surprisingly, cortistatin-deficient mice were partially resistant to EAE and other inflammatory disorders, despite showing competent inflammatory/autoreactive responses. This unexpected phenotype was associated with elevated circulating glucocorticoids and an anxiety-like behavior. Our findings provide a powerful rationale for the assessment of the efficacy of cortistatin as a novel multimodal therapeutic approach to treat multiple sclerosis and identify cortistatin as a key endogenous component of neuroimmune system.
Although necessary to eliminate pathogens, inflammation can lead to serious deleterious effects in the host if left unchecked. During the inflammatory response, further damage may arise from potential autoimmune responses occurring when the immune cells and molecules that respond to pathogen-derived antigens also react to self-antigens. In this sense, the identification of endogenous factors that control exacerbated immune responses is a key goal for the development of new therapeutic approaches for inflammatory and autoimmune diseases. Some neuropeptides that are produced during the ongoing inflammatory response have emerged as endogenous anti-inflammatory agents that could collaborate in tuning the balanced steady state of the immune system. These neuropeptides participate in maintaining immune tolerance through two distinct mechanisms: by regulating the balance between pro-inflammatory and anti-inflammatory factors, and by inducing the emergence of regulatory T cells with suppressive activity against autoreactive T cell effectors. Indeed, a functioning neuropeptide system contributes to general health, and alterations in the levels of these neuropeptides and/or their receptors lead to changes in susceptibility to inflammatory and autoimmune diseases. Recently, we found that some neuropeptides also have antimicrobial and antiparasitic actions, suggesting that they could act as primary mediators of innate defense, even in the most primitive organisms. In this review, we use the vasoactive intestinal peptide as example of an immunomodulatory neuropeptide to summarize the most relevant data found for other neuropeptides with similar characteristics, including adrenomedullin, urocortin, cortistatin and ghrelin.
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