Psoriasis is a chronic inflammatory skin disease. IL-23 plays a critical role in its pathogenesis by inducing production of IL-17A from pathological Th17 cells and IL-17A-producing γδ T cells. However, the mechanisms regulating the IL-23/IL-17 axis in psoriasis are incompletely understood.
View Article and Find Full Text PDFPsoriasis is a chronic inflammatory skin disease. IL-23 plays a critical role in its pathogenesis by inducing production of IL-17A from pathological Th17 cells and IL-17A-producing γδ T cells. However, the mechanisms regulating the IL-23/IL-17 axis in psoriasis are incompletely understood.
View Article and Find Full Text PDFMonoclon Antib Immunodiagn Immunother
April 2021
DNAM-1 is an activating immunoreceptor expressed on hematopoietic cells, including both CD4 and CD8 T cells, natural killer cells, and platelets. Since DNAM-1 is involved in the pathogenesis of various inflammatory diseases and cancers in humans as well as mouse models, it is a potential target for immunotherapy for these diseases. In this study, we generated a humanized neutralizing antihuman DNAM-1 monoclonal antibody (mAb), named TNAX101A, which contains an engineered Fc portion of human IgG1 to reduce Fc-mediated effector functions.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
July 2017
OBJECT Indoleamine 2,3-dioxygenase (IDO), a key enzyme of tryptophan (Trp) metabolism, is involved in tumor-derived immune suppression through depletion of Trp and accumulation of the metabolite kynurenine, resulting in inactivation of natural killer cells and generation of regulatory T cells (Tregs). It has been reported that high expression of IDO in cancer cells is associated with suppression of the antitumor immune response and is consistent with a poor prognosis. Thus, IDO may be a therapeutic target for malignant cancer.
View Article and Find Full Text PDFAsian Pac J Allergy Immunol
June 2014
Background & Aims: The circadian clock drives daily rhythms in behavior and physiology. A recent study suggests that intestinal permeability is also under control of the circadian clock. However, the precise mechanisms remain largely unknown.
View Article and Find Full Text PDFBackground: Cytokines in breast milk may play crucial roles in the beneficial effects of breastfeeding in protecting against allergic and infectious diseases in infants. In particular, breast milk-borne transforming growth factor-beta (TGF-β) has an important potential role in developing the mucosal immune system in infants. However, little is known about what factors influence TGF-β expression in human milk.
View Article and Find Full Text PDFAtg8 and its mammalian homolog LC3, ubiquitin-like proteins (Ubls) required for autophagosome formation, are remarkably unique in that their conjugation target is the lipid phosphatidylethanolamine (PE). Although PE was identified as the sole lipid conjugated with Atg8/LC3 in vivo, phosphatidylserine (PS) can be also a good substrate for its conjugation reaction in vitro. This posed a simple, intriguing question: What confers substrate specificity to lipidation of Atg8/LC3 in vivo? Our recent in vitro studies propose that intracellular milieus such as cytosolic pH and acidic phospholipids in membranes significantly contribute to selective production of the Atg8-PE conjugate.
View Article and Find Full Text PDFYeast Atg8 and its mammalian homolog LC3 are ubiquitin-like proteins involved in autophagy, a primary pathway for degradation of cytosolic constituents in vacuoles/lysosomes. Whereas the lipid phosphatidylethanolamine (PE) was identified as the sole in vivo target of their conjugation reactions, in vitro studies showed that the same system can mediate the conjugation of these proteins with phosphatidylserine as efficiently as with PE. Here, we show that, in contrast to PE conjugation, the in vitro phosphatidylserine conjugation of Atg8 is markedly suppressed at physiological pH.
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