Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational andin vitrostudies as well asin vivoanimal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players.

Significance: Our findings demonstrate that metabolic supplementation of mucosal T cells, isolated from patients with active ulcerative colitis (UC), with N -acetylglucosamine (GlcNAc) leads to the enhancement of branched N-glycosylation on the T cell receptor, which was associated with the control of T cell activation and function. These results were validated in “glycoengineered” mouse models with severe colitis. Overall, our results open new avenues for a targeted-specific therapy in inflammatory bowel disease (IBD). The therapeutic use of GlcNAc (either alone or in combination with other antiinflammatory therapies) represents a simple immunomodulatory strategy in IBD, with absence of side effects, low costs, and the possibility of being used as a simple rescue therapy to avoid unnecessary toxic effects and step-up therapies in IBD.

Human NK cells can respond rapidly to Plasmodium falciparum-infected RBC (iRBC) to produce IFN-γ. In this study, we have examined the heterogeneity of this response among malaria-naive blood donors. Cells from all donors become partially activated (up-regulating CD69, perforin, and granzyme) upon exposure to iRBC but cells from only a subset of donors become fully activated (additionally up-regulating CD25, IFN-γ, and surface expression of lysosomal-associated membrane protein 1 (LAMP-1)). Although both CD56^dim and CD56^bright NK cell populations can express IFN-γ in response to iRBC, CD25 and LAMP-1 are up-regulated only by CD56^dim NK cells and CD69 is up-regulated to a greater extent in this subset; by contrast, perforin and granzyme A are preferentially up-regulated by CD56^bright NK cells. NK cells expressing IFN-γ in response to iRBC always coexpress CD69 and CD25 but rarely LAMP-1, suggesting that individual NK cells respond to iRBC either by IFN-γ production or cytotoxicity. Furthermore, physical contact with iRBC can, in a proportion of donors, lead to NK cell cytoskeletal reorganization suggestive of functional interactions between the cells. These observations imply that individuals may vary in their ability to mount an innate immune response to malaria infection with obvious implications for disease resistance or susceptibility.

MiR-195 in human primary mesenchymal stromal/stem cells regulates proliferation, osteogenesis and paracrine effect on angiogenesis