Interleukin 21 Receptor Affects Adipogenesis of Human Adipose-Derived Stem/Stromal Cells

Dysfunctions in adipose tissue cells are responsible for several obesity-related metabolic diseases. Understanding the process of adipocyte formation is thus fundamental for understanding these diseases. The adipocyte differentiation of adipose-derived stem/stromal cells (ADSCs) showed a reduction in the mRNA level of the interleukin 21 receptor (IL21R) during this process. Although the receptor has been associated with metabolic diseases, few studies have examined its function in stem cells. In this study, we used confocal immunofluorescence assays to determine that IL21R colocalizes with mitochondrial protein ATP5B, ALDH4A1, and the nucleus of human ADSCs. We demonstrated that silencing and overexpression of IL21R did not affect the cell proliferation and mitochondrial activity of ADSCs. However, IL21R silencing did reduce ADSC adipogenic capacity. Further studies are needed to understand the mechanism involved between IL21R and the adipogenic differentiation process.

MicroRNA-30b Is Both Necessary and Sufficient for Interleukin-21 Receptor-Mediated Angiogenesis in Experimental Peripheral Arterial Disease

The interleukin-21 receptor (IL-21R) can be upregulated in endothelial cells (EC) from ischemic muscles in mice following hind-limb ischemia (HLI), an experimental peripheral arterial disease (PAD) model, blocking this ligand–receptor pathway-impaired STAT3 activation, angiogenesis, and perfusion recovery. We sought to identify mRNA and microRNA transcripts that were differentially regulated following HLI, based on the ischemic muscle having intact, or reduced, IL-21/IL21R signaling. In this comparison, 200 mRNAs were differentially expressed but only six microRNA (miR)/miR clusters (and among these only miR-30b) were upregulated in EC isolated from ischemic muscle. Next, myoglobin-overexpressing transgenic (MgTG) C57BL/6 mice examined following HLI and IL-21 overexpression displayed greater angiogenesis, better perfusion recovery, and less tissue necrosis, with increased miR-30b expression. In EC cultured under hypoxia serum starvation, knock-down of miR-30b reduced, while overexpression of miR-30b increased IL-21-mediated EC survival and angiogenesis. In Il21r−/− mice following HLI, miR-30b overexpression vs. control improved perfusion recovery, with a reduction of suppressor of cytokine signaling 3, a miR-30b target and negative regulator of STAT3. Together, miR-30b appears both necessary and sufficient for IL21/IL-21R-mediated angiogenesis and may present a new therapeutic option to treat PAD if the IL21R is not available for activation.

Peran Reseptor IL-21 (IL-21R) sebagai Target Terapi Pada Penyakit Arteri Perifer

Background: Peripheral Artery Disease (PAD) is caused due to the disruption of blood supply to the periphery caused by blockages in the arteries. PAD is a disease that is difficult to detect and the current therapy is still limited to pharmacological therapy to reduce the risk of PAP incidence and surgical therapy if complications of PAD arise. The interleukin-21 receptor (IL-21R) is a family of interleukins that has been widely studied for its role in many diseases. Objectives: The aim of this review is to discuss the effect of IL-21R on the pathogenesis of PAP. Methods: A literature search was performed with PubMed, Google Scholar, and ScienceDirect using the keywords “peripheral artery disease”, “interleukin-21 receptor”, “inflammation”, “angiogenesis”, and “therapy”. Discussion: PAD can arise due to the formation of atherosclerotic plaques that block arteries so that blood supply is impaired. In the case of PAD, activation of IL-21R has the ability to stimulate angiogenesis thereby modulating the perfusion of hypoxic tissues in cases of PAD. Further research is needed regarding IL-21R activity in the future to study the potential of IL-21R for the more effective treatment of PAD cases in the future. Conclusion: IL-21R can activate angiogenesis and avoid further tissue damage in PAP. Keywords: interleukin-21 receptors, peripheral artery disease, therapy Latar Belakang: Penyakit Arteri Perifer (PAP) disebabkan karena gangguan suplai darah ke bagian perifer yang disebabkan karena sumbatan pada pembuluh darah arteri. PAP merupakan penyakit yang sulit terdeteksi dan terapi yang ada saat ini masih terbatas pada terapi farmakologis untuk menurunkan risiko kejadian PAP dan terapi pembedahan apabila timbul komplikasi PAP. Reseptor interleukin-21 (IL-21R) merupakan salah satu famili interleukin yang telah banyak dipelajari terkait perannya pada banyak penyakit. Tujuan: Tujuan dari tinjauan ini adalah untuk membahas pengaruh IL-21R terhadap perjalanan penyakit PAP. Metode: Pencarian literatur dilakukan dengan PubMed, Google Scholar, dan ScienceDirect menggunakan kata kunci “peripheral artery disease”, “reseptor interleukin-21”, “inflamasi”, ”angiogenesis”, dan “terapi”. Pembahasan: PAP dapat timbul karena pembentukan plak aterosklerosis yang menyumbat pembuluh darah arteri sehingga suplai darah terganggu. Pada kasus PAP, aktivasi IL-21R memiliki kemampuan untuk menstimulasi angiogenesis sehingga memodulasi perfusi jaringan yang mengalami hipoksia pada kasus PAP. Masih diperlukan penelitian lebih lanjut mengenai aktivitas IL-21R di masa depan untuk mempelajari potensi IL-21R untuk pengobatan kasus PAP yang lebih efektif di masa depan. Kesimpulan: IL-21R dapat mengaktivasi angiogenesis dan menghindari kerusakan jaringan lebih lanjut pada PAP. Kata Kunci: penyakit arteri perifer, reseptor interleukin-21, terapi

The Role of T Follicular Helper Cells and Interleukin-21 in the Pathogenesis of Inflammatory Bowel Disease

T follicular helper (Tfh) cells represent a novel subset of CD4+ T cells which can provide critical help for germinal center (GC) formation and antibody production. The Tfh cells are characterized by the expression of CXC chemokine receptor 5 (CXCR5), programmed death 1 (PD-1), inducible costimulatory molecule (ICOS), B cell lymphoma 6 (BCL-6), and the secretion of interleukin-21 (IL-21). Given the important role of Tfh cells in B cell activation and high-affinity antibody production, Tfh cells are involved in the pathogenesis of many human diseases. Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases characterized by symptoms such as diarrhea, abdominal pain, and weight loss. Ulcerative colitis (UC) and Crohn’s disease (CD) are the most studied types of IBD. Dysregulated mucosal immune response plays an important role in the pathogenesis of IBD. In recent years, many studies have identified the critical role of Tfh cells and IL-21 in the pathogenic process IBD. In this paper, we will discuss the role of Tfh cells and IL-21 in IBD pathogenesis.