Mesenchymal stem cells are culture-derived mesodermal progenitors isolatable from all vascularized tissues. In spite of multiple fundamental, pre-clinical and clinical studies, the native identity and role in tissue repair of MSCs have long remained elusive, with MSC selection in vitro from total cell suspensions essentially unchanged as a mere primary culture for half a century. Recent investigations have helped understand the tissue origin of these progenitor cells, and uncover alternative effects of MSCs on tissue healing via growth factor secretion and interaction with the immune system. In this review, we describe current trends in MSC biology and discuss how these may improve the use of these therapeutic cells in tissue engineering and regenerative medicine.

Metabolic disorders, such as obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease, are characterized by chronic low-grade tissue and systemic inflammation. During obesity, the adipose tissue undergoes immunometabolic and functional transformation. Adipose tissue inflammation is driven by innate and adaptive immune cells and instigates insulin resistance. Here, we discuss the role of innate immune cells, that is, macrophages, neutrophils, eosinophils, natural killer cells, innate lymphoid type 2 cells, dendritic cells, and mast cells, in the adipose tissue in the healthy (lean) and diseased (obese) state and describe how their function is shaped by the obesogenic microenvironment, and humoral, paracrine, and cellular interactions. Moreover, we particularly outline the role of hypoxia as a central regulator in adipose tissue inflammation. Finally, we discuss the long-lasting effects of adipose tissue inflammation and its potential reversibility through drugs, caloric restriction, or exercise training.

A lack of regulatory T cell function is a critical factor in the pathogenesis of autoimmune diseases, such as multiple sclerosis (MS). Ligation of the complement regulatory protein CD46 facilitates the differentiation of T helper 1 (T1) effector cells into interleukin-10 (IL-10)-secreting type 1 regulatory T cells (Tr1 cells), and this pathway is defective in MS patients. Cleavage of the ectodomain of CD46, which contains three N-glycosylation sites and multiple O-glycosylation sites, enables CD46 to activate T cells. We found that stimulation of the T cell receptor (TCR)-CD3 complex was associated with a reduction in the apparent molecular mass of CD46 in a manner that depended on O-glycosylation. CD3-stimulated changes in CD46 O-glycosylation status reduced CD46 processing and subsequent T cell signaling. During T cell activation, CD46 was recruited to the immune synapse in a manner that required its serine-, threonine-, and proline-rich (STP) region, which is rich in O-glycosylation sites. Recruitment of CD46 to the immune synapse switched T cells from producing the inflammatory cytokine interferon-γ (IFN-γ) to producing IL-10. Furthermore, CD4 T cells isolated from MS patients did not exhibit a CD3-stimulated reduction in the mass of CD46 and thus showed increased amounts of cell surface CD46. Together, these data suggest a possible mechanism underlying the regulatory function of CD46 on T cells. Our findings may explain why this pathway is defective in patients with MS and provide insights into MS pathogenesis that could help to design future immunotherapies.