Studies on the role of interleukins (ILs) in autoimmune and inflammatory diseases allow for the better understanding of pathologic mechanisms of disease and reshaping of treatment modalities. The development of monoclonal antibodies targeting specific ILs or IL signaling pathways (i.e., anti‐IL‐17/IL‐23 in psoriasis or anti‐IL‐4/IL‐13 in atopic dermatitis) is the shining example of therapeutic interventions in research. IL‐21, belonging to the group of ɣc‐cytokines (IL‐2, IL‐4, IL‐7, IL‐9, and IL‐15), is gaining attention for its pleiotropic role in several types of immune cells as activator of various inflammatory pathways. In both health and disease, IL‐21 sustains T‐ and B‐cell activity. Together with IL‐6, IL‐21 helps to generate Th17 cells, promotes CXCR5 expression in T cells, and their maturation into follicular T helper cells. In B cells, IL‐21 sustains their proliferation and maturation into plasma cells and promotes class switching and antigen‐specific antibody production. Due to these characteristics, IL‐21 is a main factor in numerous immunologic disorders, such as rheumatoid arthritis and MS. Studies in preclinical skin disease models and on human skin strongly suggest that IL‐21 is crucially involved in inflammatory and autoimmune cutaneous disorders. Here, we summarize the current knowledge of IL‐21 in well‐known skin diseases.

Activation of brown adipose tissue may increase energy expenditure by non-shivering thermogenesis. Cold exposure is one of the options to activate brown adipocytes. To link changes in energy metabolism with microRNA expression (miRNAs), we analyzed 158 miRNAs in serum of 169 healthy individuals before and after cold exposure. Validating the results of a miRNA array, a significant down-regulation of miR-375 after cold exposure (P < 0.0001) was detected. These changes went along with a significant negative correlation between miR-375 and visceral adipose tissue (VAT) mass (P < 0.0001), implicating a specific function of miR-375 in this depot. Significantly higher expression levels of miR-375 were found in VAT in comparison to subcutaneous fat (SAT). Using in silico prediction, we identified putative miR-375 target genes involved in the thermogenesis pathway. Cold-stimulation of subcutaneous and visceral pre-adipocytes (PACs) led to significantly higher expression levels of FABP4, FGF21, PPARGC1A and PRDM16 in VC-PACs. Analyzing miR-375 knock down and cold stimulated VC-PACs revealed a significant up-regulation of thermogenesis associated genes PPARGC1A, ELOVL3 and PRDM16. In summary, our findings identified miR-375 as a potential adipogenic and thermogenesis-associated miRNA exclusively acting in visceral adipose tissue.