Immunity Zhejiang University Jin Jin/Cao Qian discovered selenium as a potential treatment for patients with Crohn's disease

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iNature inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC)
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Immune disorders play a vital role in the pathogenesis of these two types of IBD, but the differences in the immune microenvironment of the colon and its underlying mechanisms are still lacking in research
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On August 2, 2021, Jin Jin and Cao Qian of Zhejiang University jointly published a research paper entitled "Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn's disease" in Immunity.
The analysis examined the immunological characteristics and metabolic microenvironment of individuals with untreated IBD
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 The regulation of CD-specific metabolites, especially reduced selenium, can significantly shape the differentiation of type 1 T helper (Th1) cells, which are particularly enriched in CD
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Selenium supplements suppress the symptoms and onset of CD and Th1 cell differentiation through selenoprotein W (SELW)-mediated elimination of cellular reactive oxygen species
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SELW promotes the purine salvage pathway and inhibits single-carbon metabolism by recruiting E3 ubiquitin ligase, protein 21 containing a triple motif, which controls the stability of serine hydroxymethyltransferase 2
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The work of this research emphasizes that selenium is an important regulator of T cell response and a potential therapeutic target in CD
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In addition, on January 13, 2021, Jin Jin of Zhejiang University and Li Yiyuan of Southeast University jointly published a research paper entitled "Substrate-specific recognition of IKKs mediated by USP16 facilitates autoimmune inflammation" in Science Advances.
The research found that lysine Ubiquitination of IKKβ on 238 is significantly increased during inflammation
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Using mass spectrometry, this study determined that USP16 is an important regulator of IKKβ ubiquitination levels, which selectively affects p105 phosphorylation without directly affecting p65 or IκBα phosphorylation
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In addition, USP16 is highly expressed in colonic macrophages of IBD patients, while the myeloid-conditioned USP16 knockout mice showed reduced IBD severity
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This research provides a new theoretical basis for the pathogenesis of IBD and targeted precision intervention therapy (click to read)
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On October 31, 2019, Jin Jin of Zhejiang University and Renjie Chai of Southeast University jointly published a research paper titled "Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior" in Cell Online, indicating the lack of CD4 + T cells protect mice from stress-induced anxiety-like behaviors
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Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4 + T cells, which in turn leads to various behavioral abnormalities, including anxiety, depression, and social disorders
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This study hints at a key link between the disorder of purine metabolism in CD4 + T cells and stress-driven anxiety-like behaviors
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All in all, the study determined that peripheral CD4 + T cells are the key mediator of stress-induced mood disorders
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In the future, it will become interesting to clarify whether specific CD4 + T cell subsets regulate the mood and behavior of patients with anxiety disorders
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 The findings of this research are of far-reaching significance for the development of valuable treatments for various psychiatric and metabolic diseases (click to read)
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Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC), which is characterized by chronic and recurrent bowel inflammation
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In newly industrialized countries, the incidence of IBD is increasing
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In addition to chronic intestinal inflammation, these two diseases show different clinical and histopathological features
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The pathogenesis of IBD has not been studied in depth
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A variety of factors, such as genetic mutations, diet, intestinal microbial disorders, and excessive immune activation, are all related to the pathogenesis of IBD
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Among these factors, dysfunction of the mucosal immune system is the most important factor in the pathogenesis of CD and UC
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Some previous evidence indicates that there are some obvious differences in the immune microenvironment between these two types of IBD, especially the T cell differentiation pattern
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However, individuals included in different studies have received various medications, such as aminosalicylates, steroids, immunomodulators, or biological agents, which can affect their pathological immune responses
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Therefore, there is still a lack of research on the pathological features of the immune response in IBD
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The increase in the incidence of IBD in newly industrialized countries may be related to the process of urbanization and changes in diet
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Current research emphasizes that short-chain fatty acids, tryptophan and bile acids are involved in mucosal immune homeostasis and the onset of IBD
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Metabolites are key mediators that regulate T cell function
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The metabolic process produces abundant intermediate metabolites and by-products, such as reactive oxygen species (ROS), which play an important role in regulating T cell function and metabolic changes
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The concentration of ROS is strictly controlled by the antioxidant system, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPxs), thioredoxin reductase (TrxRs) And glutathione reductase (GR)
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It is worth noting that some non-enzymatic molecules, such as reduced glutathione (GSH), uric acid and ascorbic acid, can also react with ROS
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However, the relationship between ROS and antioxidant molecules and different T cell differentiation and IBD pathogenesis remains unclear
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Article pattern (picture from Immunity) Selenium is an essential trace mineral that can combine with protein to form selenoprotein, which plays an indispensable role in ROS clearance and redox regulation
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Among the 25 selenoproteins identified in humans, GPxs and TrxRs are recognized antioxidant enzymes, while the physiological functions of other selenoproteins (for example, selenoprotein W [SELW], SelT, and SelH) have not been fully characterized
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Several studies have established selenium deficiency in patients with IBD, as evidenced by a decrease in serum selenoprotein P (SePP1)
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In the mouse colitis model, selenium deficiency can exacerbate intestinal damage and promote inflammation
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However, research on specific selenoproteins that affect T cell function in IBD is still lacking
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Here, the study shows a series of disease-specific immune cell types and metabolite changes in the pathogenesis of CD and UC
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The study found that selenium was specifically and severely reduced in CD mucosa, and selenium supplementation significantly inhibited Th1 cell differentiation in vitro and in vivo
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Selenium promotes the induction of SELW and significantly eliminates cytoplasmic ROS
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Selenium supplementation can inhibit the severity of colitis induced by adoptive T cell transfer and the clinical symptoms of CD patients
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These findings establish selenium as a potential treatment for patients with CD
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