No abstract

Myeloid C‐type lectin receptors (CLRs), which consist of an extracellular carbohydrate recognition domain and intracellular signal transducing motif such as the immunoreceptor tyrosine‐based activation motif (ITAM) or immunoreceptor tyrosine‐based inhibitory motif (ITIM), are innate immune receptors primarily expressed on myeloid lineage cells such as dendritic cells (DCs) and Mϕs. CLRs play important roles in host defense against infection by fungi and bacteria by recognizing specific carbohydrate components of these pathogens. However, these immune receptors also make important contributions to immune homeostasis of mucosa and skin in mammals by recognizing components of microbiota, as well as by recognizing self‐components such as alarmins from dead cells and noncanonical non‐carbohydrate ligands. CLR deficiency not only induces hypersensitivity to infection, but also causes dysregulation of muco‐cutaneous immune homeostasis, resulting in the development of allergy, inflammation, autoimmunity, and tumors. In this review, we introduce recent discoveries regarding the roles of myeloid CLRs in the immune system exposed to the environment, and discuss the roles of these lectin receptors in the development of colitis, asthma, psoriasis, atopic dermatitis, and cancer. Although some CLRs are suggested to be involved in the development of these diseases, the function of CLRs and their ligands still largely remain to be elucidated.

Dectin-1 (gene Clec7a), a receptor for β-glucans, plays important roles in the host defense against fungi and immune homeostasis of the intestine. Although this molecule is also suggested to be involved in the regulation of tumorigenesis, the role in intestinal tumor development remains to be elucidated. In this study, we find that azoxymethane-dextran-sodium-sulfate-induced and ApcMin-induced intestinal tumorigenesis are suppressed in Clec7a−/− mice independently from commensal microbiota. Dectin-1 is preferentially expressed on myeloid-derived suppressor cells (MDSCs). In the Clec7a−/− mouse colon, the proportion of MDSCs and MDSC-derived prostaglandin E2 (PGE2) levels are reduced, while the expression of IL-22 binding protein (IL-22BP; gene Il22ra2) is upregulated. Dectin-1 signaling induces PGE2-synthesizing enzymes and PGE2 suppresses Il22ra2 expression in vitro and in vivo. Administration of short chain β-glucan laminarin, an antagonist of Dectin-1, suppresses the development of mouse colorectal tumors. Furthermore, in patients with colorectal cancer (CRC), the expression of CLEC7A is also observed in MDSCs and correlated with the death rate and tumor severity. Dectin-1 signaling upregulates PGE2-synthesizing enzyme expression and PGE2 suppresses IL22RA2 expression in human CRC-infiltrating cells. These observations indicate a role of the Dectin-1-PGE2-IL-22BP axis in regulating intestinal tumorigenesis, suggesting Dectin-1 as a potential target for CRC therapy.

Field of the paper: Immunology Original paperThe C-type lectin receptor Clec1A plays an important role in the development of experimental autoimmune encephalomyelitis by enhancing antigen presenting ability of dendritic cells and inducing inflammatory cytokine IL-17

The article considers the problems of assessing the program of additional vocational education, considering the new realities, the management environment, the widespread introduction of the digital economy, which place new demands on workers and their professional competencies or even changes in their work activities. A methodology is proposed for calculating the integrated index of the educational program effectiveness, including vocational education, considering important economic, social, organizational, and educational components, which involves considering their quantitative and qualitative characteristics. The main conceptual elements of the evaluation system of additional programs are reflected, and the scale and evaluation standards are proposed. The economic effect of the program is determined in cost terms based on the expected revenues and expenses for the program. The article shows an example of calculating private indicators of the effectiveness of educational programs for additional vocational training, and their translation into the relative effect is carried out with the help of the profitability indicator. This allows choosing the educational product necessary for specific consumers to attract additional extra-budgetary funds for the development of science in educational institutions. In addition, the issue of training the necessary personnel in demand for business is being addressed. According to societal needs, personnel with specified professional competencies appear on the labor market. All this creates conditions for realizing the interests of employees, employers, and the state.