Protective role of colitis in inflammatory arthritis via propionate-producing Bacteroides in the gut.

Objectives: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events. Methods: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated propionate-deficient mutant bacteria. Short-chain fatty acids were measured in the bacterial culture supernatant, serum, feces, and cecum contents using gas chromatography-mass spectrometry. Mice fed with candidate and mutant bacteria were subjected to inflammatory arthritis. Results: Contrary to expectations, the mice treated with DSS exhibited fewer symptoms of inflammatory arthritis. Intriguingly, the gut microbiota contributes, at least in part, to the improvement of colitis-mediated arthritis. Among the altered microorganisms, Bacteroides vulgatus and its higher taxonomic ranks were enriched in the DSS-treated mice. B. vulgatus, B. caccae, and B. thetaiotaomicron exerted anti-arthritic effects. Propionate production deficiency further prevented the protective effect of B. thetaiotaomicron on arthritis. Conclusions: We suggest a novel relationship between the gut and joints and an important role of the gut microbiota as communicators. Moreover, the propionate-producing Bacteroides species examined in this study may be a potential candidate for developing effective treatments for inflammatory arthritis.

Mycobacterium potentiates protection from colorectal cancer by gut microbial alterations.

Not only are many Mycobacteria pathogens, but they can act as strong non-specific immunopotentiators, generating beneficial effects on the pathogenesis of some diseases. However, there has been no direct evidence of the effect of mycobacterial species on colorectal cancer (CRC). Herein, we showed that there may be a meaningful inverse correlation between the incidence of tuberculosis and CRC based on global statistics and that heat-killed Mycobacterial tuberculosis and live Mycobacterium bovis (Bacillus Calmette-Guérin strain) could ameliorate CRC development. In particular, using a faecal microbiota transplantation and a comparison between separate housing and cohousing, we demonstrated that the gut microbiota is involved in the protective effects. The microbial alterations can be elucidated by the modulation of antimicrobial activities including those of the Reg3 family genes. Furthermore, interleukin-22 production by T helper cells contributed to the anti-inflammatory activity of Mycobacteria. Our results revealed a novel role of Mycobacteria involving gut microbial alterations in dampening inflammation-associated CRC and an immunological mechanism underlying the interaction between microbes and host immunity.

RNA Metabolism in T Lymphocytes.

RNA metabolism plays a central role in regulating of T cell-mediated immunity. RNA processing, modifications, and regulations of RNA decay influence the tight and rapid regulation of gene expression during T cell phase transition. Thymic selection, quiescence maintenance, activation, differentiation, and effector functions of T cells are dependent on selective RNA modulations. Recent technical improvements have unveiled the complex crosstalk between RNAs and T cells. Moreover, resting T cells contain large amounts of untranslated mRNAs, implying that the regulation of RNA metabolism might be a key step in controlling gene expression. Considering the immunological significance of T cells for disease treatment, an understanding of RNA metabolism in T cells could provide new directions in harnessing T cells for therapeutic implications.

Water Extract of Artemisia annua L. Exhibits Hepatoprotective Effects Through Improvement of Lipid Accumulation and Oxidative Stress-Induced Cytotoxicity.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease with a complex underlying mechanism that has not been completely understood. Thus, effective and safe drugs for this disease are not yet available. Artemisia annua L. is a medicinal plant with potent antimicrobial and antioxidant activities. In this study, we prepared a water extract of A. annua (WEAA) and examined its potential for NAFLD treatment. First, we pretreated HepG2 cells (human hepatocarcinoma cell line) with WEAA and then treated the cells with oleic acid or tert-butylhydroperoxide to examine the effect of WEAA on the lipid accumulation and the cytotoxicity, respectively. WEAA not only inhibited lipid accumulation within HepG2 cells but also protected cells from oxidative stress-mediated damage through the activation of antioxidant enzymes (such as activation of superoxide dismutase and production of glutathione) and its own scavenging activity. Next, to confirm protective effect of the WEAA in in vivo, mice were intragastrically administered with WEAA, extract of Silybum marianum or water once a day, and simultaneously provided with high-fat diet to induce fatty liver and hepatic steatosis. Oral administration of WEAA ameliorated weight gain and hepatic lipid accumulation in high-fat diet-fed mice. Moreover, the plasma levels of triglyceride, aspartate aminotransferase, and alanine aminotransferase were reduced in the WEAA-treated group. Our findings indicated that WEAA may be a potential intervention for preventing or treating hepatic lipid accumulation and liver damage.

Regulation of chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis.

Chitinase-3-like-1 (Chi3l1) is known to play a significant role in the pathogenesis of Type 2 inflammation and cancer. However, the function of Chi3l1 in T cell and its clinical implications are largely unknown. Here we show that Chi3l1 expression was increased in activated T cells, especially in Th2 cells. In addition, Chi3l1-deficient T cells are hyper-responsive to TcR stimulation and are prone to differentiating into Th1 cells. Chi3l1-deficient Th1 cells show increased expression of anti-tumor immunity genes and decreased Th1 negative regulators. Deletion of Chi3l1 in T cells in mice show reduced melanoma lung metastasis with increased IFNγ and TNFα-producing T cells in the lung. Furthermore, silencing of Chi3l1 expression in the lung using peptide-siRNA complex (dNP2-siChi3l1) efficiently inhibit lung metastasis with enhanced Th1 and CTL responses. Collectively, this study demonstrates Chi3l1 is a regulator of Th1 and CTL which could be a therapeutic target to enhance anti-tumor immunity.