China
Africa
Explore chapters and articles related to this topic
Innate lymphoid cells
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
In contrast, when a tissue is infected by extracellular microbes such as bacteria and fungi, APCs react by producing IL-1β and IL-23. These inducer cytokines promote the differentiation of TH17 cells and ILC3s and activate their expression of IL-17, IL-22, GM-CSF and lymphotoxin. These cytokines lead to the recruitment of phagocytes, such as neutrophils, that clear the microbes, and also induce the production of antimicrobial proteins (AMPs) by epithelial cells and stromal cells. The transcription factor RORγt is required for the generation of ILC3s and TH17 cells, and its expression defines these cells.
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
IL17, which is considered one of the central players in both psoriasis and the angiogenesis of psoriasis, is now known to be secreted to a large extent by neutrophils in the psoriatic epidermis, rather than Th17 cells. Neutrophils can also be associated with RORγt—the transcription factor associated with Th17. The IL17 secretion by neutrophil is possibly secreted along with the neutrophil extracellular trap (NET) (Lin 2011). NETs, discovered in 2004, produced by NETosis or ETosis, are the active cellular process of throwing out DNA, along with specific subsets of primary, secondary, and tertiary granule contents, especially many antimicrobial proteins (Brinkmann et al. 2004). This was originally thought to be a form of cell death but was later found to also be possible without cell death, and mitochondrial DNA, rather than genomic DNA, is thrown out in this “vital” form of NETosis. NETs are rich in many known intracellular self-antigens and are also known to be able to stimulate angiogenesis itself.
Retinoic acid-related orphan receptor gamma t (RORγt) inverse agonists/antagonists for the treatment of inflammatory diseases – where are we presently?
Published in Expert Opinion on Drug Discovery, 2021
Retinoic acid receptor-related orphan nuclear receptors (RORs) are transcription factors which belong to the steroid/thyroid hormone nuclear receptor superfamily [1–3]. RORγt is exclusively expressed in the cells of the immune system (e.g., T helper cells, thymocytes and lymphoid tissue inducer cells). RORγt has been identified as the master regulator of TH17 cell differentiation and IL-17A production, as well as IL-17F and IL-22, in both innate and adaptive immune cells [4]. IL-17A is a pro-inflammatory cytokine that contributes to chronic inflammation associated with multiple diseases including psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease and multiple sclerosis (MS) [5]. Biologics that target the IL-23/IL-17 pathway have shown significant clinical efficacy in the treatment of inflammatory diseases [6,7]. Therefore, RORγt has emerged as a potentially important small molecule target for intervention in this disease-relevant pathway.
The Inhibitory Effects of Pentacyclic Triterpenes from Loquat Leaf against Th17 Differentiation
Published in Immunological Investigations, 2020
Xiaoqing Zhou, Huanpeng Chen, Fengjiao Wei, Qingyu Zhao, Qiao Su, Yu Lei, Meng Yin, Xuyan Tian, Zhonghua Liu, Bolan Yu, Chuan Bai, Xixin He, Zhaofeng Huang
Retinoic acid receptor-related orphan receptor gamma t (RORγt) is very important for Th17 cell differentiation. Deficiency of RORγt can alleviate the manifestation of many autoimmune disorders, such as experimental allergic encephalomyelitis (EAE), SLE, and rheumatoid arthritis (RA) (He et al. 2017; Huang et al. 2015; Isono et al. 2014). Some studies have reported that small-molecule inhibitors may prevent the development of the autoimmune disease by inhibiting RORγt activity or secretion of Th17-related inflammatory factors. For example, digoxin can inhibit Th17 activity and decrease the clinical score and mortality rate of EAE and CIA (Huh et al. 2011; Lee et al. 2015).
Retinoic acid receptor-related orphan receptor gamma-t (RORγt) inhibitors in clinical development for the treatment of autoimmune diseases: a patent review (2016-present)
Published in Expert Opinion on Therapeutic Patents, 2019
Nannan Sun, Huimin Guo, Yonghui Wang
The nuclear receptor (NR) retinoic acid receptor-related orphan receptor-gamma (RORγ or RORc, also known as NR1F3) is the most recently found member of ROR subfamily, following the previously identified member RORα (NR1F1) and RORβ (NR1F2). Two isoforms of RORγ exist: RORγ (RORγ1) and RORγt (RORγ2) [1,2]. Different from RORγ, RORγt is present mainly in thymus, and it plays a key role in the proliferation of Th17 cell, and the production of the pro-inflammatory cytokine IL-17 [3]. Tissue-specific expression of RORγt indicates its special role in the development and regulation of the immune system [4]. RORγt-/- mice had no discernible physical defect, but there is a potential risk of high incidence of T-cell lymphomas [5]. Further study reported that RORγt-/- mice develop lymphoma in a similar time frame as embryonic Rorc knockouts, and also suggests in mice where the gene deletion is incomplete, the thymus undergoes a rapid selection process replacing Rorc deficient cells with remnant thymocytes carrying a functional locus and that subsequently, lymphoblastic lymphoma was not developed [6]. The total thymus cell numbers of RORγt−/- animals were less than half of wild-type levels [7,8]. RORγt-/- mice had attenuated autoimmune disease and lacked tissue-infiltrating Th17 cells [3,9]. Indeed, RORγt is considered as a vital regulator of immune homeostasis and a potential therapeutic target for inflammatory diseases. In recent years, many pharmaceutical companies and research institutes have paid much of attention to this target and put a lot of efforts on the discovery of RORγt inhibitors. The progression of a number of RORγt inhibitors into clinical trials suggests that RORγt is a valuable drug-target for the treatment of autoimmune diseases, especially for psoriasis.