Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases

Interleukin (IL)-24 belongs to the IL-10 family and signals through two receptor complexes, i.e., IL-20RA/IL-20RB and IL-20RB/IL22RA1. It is a multifunctional cytokine that can regulate immune response, tissue homeostasis, host defense, and oncogenesis. Elevation of IL-24 is associated with chronic inflammation and autoimmune diseases, such as psoriasis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Its pathogenicity has been confirmed by inducing inflammation and immune cell infiltration for tissue damage. However, recent studies also revealed their suppressive functions in regulating immune cells, including T cells, B cells, natural killer (NK) cells, and macrophages. The tolerogenic properties of IL-24 were reported in various animal models of autoimmune diseases, suggesting the complex functions of IL-24 in regulating autoimmunity. In this review, we discuss the immunoregulatory functions of IL-24 and its roles in autoimmune diseases.

Interluekin-6 inhibitors for the treatment of adult-onset Still’s disease

ABSTRACT Adult-onset Still’s disease is a systemic inflammatory disease characterized by high spiking fever, arthritis, evanescent skin rash, leukocytosis, and hyperferritinemia. The pathogenesis of adult-onset Still’s disease has not been fully understood yet; however, multiple proinflammatory cytokines, such as IL-1β and IL-6, play important roles in the development of adult-onset Still’s disease. IL-6 is a multifunctional cytokine that accelerates the differentiation of macrophages and cytotoxic T-cells and chemotaxis of neutrophils and macrophages. Serum concentrations of IL-6 well correlate with disease activity of adult-onset Still’s disease, and blockade of IL-6 has been proven to be effective in active adult-onset Still’s disease. This review will focus on the recent understanding of the role of proinflammatory cytokines of adult-onset Still’s disease and the efficacy of IL-6 inhibitors for the treatment of adult-onset Still’s disease.

Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression

Cancers may escape elimination by the host immune system by rewiring the tumour microenvironment towards an immune suppressive state. Transforming growth factor-β (TGF-β) is a secreted multifunctional cytokine that strongly regulates the activity of immune cells while, in parallel, can promote malignant features such as cancer cell invasion and migration, angiogenesis, and the emergence of cancer-associated fibroblasts. TGF-β is abundantly expressed in cancers and, most often, its abundance associated with poor clinical outcomes. Immunotherapeutic strategies, particularly T cell checkpoint blockade therapies, so far, only produce clinical benefit in a minority of cancer patients. The inhibition of TGF-β activity is a promising approach to increase the efficacy of T cell checkpoint blockade therapies. In this review, we briefly outline the immunoregulatory functions of TGF-β in physiological and malignant contexts. We then deliberate on how the therapeutic targeting of TGF-β may lead to a broadened applicability and success of state-of-the-art immunotherapies.

Facile synthesis of dendrimer like mesoporous silica nanoparticles to enhance targeted delivery of interleukin-22

Interleukin (IL)-22 is a multifunctional cytokine with a very short half-life (~30 min) that activates STAT3 and can elicit strong anti-inflammatory effects in the intestine but can induce inflammation in...

Relationships of interleukin-17 polymorphisms with recurrent aphthous ulcer risk in a Han Chinese population

Objective Interleukin (IL)-17 is a multifunctional cytokine with important roles in inflammatory and autoimmune diseases. This case–control study explored the relationships of IL-17A rs2275913 and IL-17F rs763780 single-nucleotide polymorphisms (SNPs) with recurrent aphthous ulcer (RAU) morbidity and severity. Methods IL-17A rs2275913 and IL-17F rs763780 SNPs were measured in 125 patients with RAU and 116 healthy control participants. The genotype distributions, disease risks, and relationships with RAU severity were analyzed. Results RAU risk was associated with rs2275913 after adjustment for age, body mass index, sex, smoking status, and drinking status (AA vs. GG: odds ratio [OR], 2.759; 95% confidence interval [CI], 1.381–5.512; A allele vs. G allele: OR, 1.783; 95% CI, 1.242–2.560). TC and CC genotypes in rs763780, and the corresponding C allele, demonstrated greater prevalence among patients with RAU, compared with the TT genotype (TC vs. TT, OR: 1.895; 95% CI: 1.088–3.301; CC vs. TT, OR: 4.080, 95% CI: 1.079–15.425; C allele vs. T allele, OR: 1.969, 95% CI: 1.257–3.083). Serum IL-17 concentrations were also higher in patients with RAU than in control participants. These concentrations were associated with IL-17 polymorphisms. Conclusions IL-17 polymorphisms might be associated with greater risk of RAU pathogenesis.