Editorial: Molecules Balancing Immunological Surveillance against Cancer and Autoimmune Diseases

The innate and the adaptive immune systems work in concert to deal with pathologies introduced by internal and external factors (e.g., viruses, bacteria, and fungi) – some of which may be associated with the development of autoimmune and cancerous cells. Mechanistically, there are internal factors that are responsible for the hypo-and hyperfunction of immune tolerance apparatus. Consequently, it could lead to the development of autoimmune diseases and malignancies, respectively. In the last decade, the study of cancer and autoimmunity suggested that these two entities might reflect two opposed extreme end-points of an immune response spectrum. Accordingly, the overexpression of certain molecules could result in malignancies, whereas deficient expression of the same molecules could lead to the development of autoimmune diseases. Two journals, Frontiers in Immunology and Frontiers in Oncology, participated in this special issue in an attempt to gain the prospective of professionals in both fields of autoimmunity and cancer, hoping to identify molecules and factors that possess dual roles with opposing effects on autoim-mune diseases and cancer. E3 ligase Cbl-b, as reviewed by Lutz-Nicoladoni et al., is central in the balance of activating and inhibitory inputs to immune cells. Specifically, Cbl-b negatively regulates activation signals through antigen or pattern recognition receptors and costimulatory molecules. Although cblb-deficient immune cells display lower activation thresholds and cblb knockout mice spontaneously develop autoimmunity and are highly susceptible to experimental autoimmunity, the increased activation potential of cblb-deficient cells renders them more potent to fight against malignancies or infections. In the study of multiple sclerosis (MS), Kaushansky and Ben-Nun, report that the allele DQB1*06:02 shown previously to be a disease-modifying allele, also plays a role as a disease-predisposing allele. They review a novel " humanized " model of MS-like disease, in which autoimmunity against myelin may be driven by a pathogenic HLA-DQ expression. This model also supports an additional target autoantigen, e.g., myelin-associated oligodendrocytic basic protein (MOBP) in the pathogenesis of MS. Haque et al. summarize the utilization of regulatory T cells (Treg cells) in treating rheumatoid arthritis (RA). Because Foxp3 can be polyubiquitinated, they show that the expression of Foxp3 in T cells can be facilitated through Foxp3 ubiquitination. Ubiquitin-specific-processing protease 7 (USP7) is an active enzyme in Treg cells, which may be associated with Foxp3, and leads to its deu-biquitination. By contrast, diminished function of USP7 results in a decreased function of Treg cells. In RA, Treg cells do not possess normal immune …