Intestinal microbiota changes in Graves' disease: a prospective clinical study.

Graves' disease (GD) occurs due to an autoimmune dysfunction of thyroid gland cells, leading to manifestations consistent with hyperthyroidism. Various studies have confirmed the link between autoimmune conditions and changes in the composition of intestinal microbial organisms. However, few studies have assessed the relationship between the GD and the changes in intestinal microbiota. Therefore, the present study aimed to investigate changes in intestinal flora that may occur in the setting of GD. Thirty-nine patients with GD and 17 healthy controls were enrolled for fecal sample collection. 16S rRNA sequencing was used to analyze the diversity and composition of the intestinal microbiota. High-throughput sequencing of 16S rRNA genes of intestinal flora was performed on Illumina Hiseq2500 platform. Comparing to healthy individuals, the number of Bacilli, Lactobacillales, Prevotella, Megamonas and Veillonella strains were increased, whereas the number of Ruminococcus, Rikenellaceae and Alistipes strains were decreased among patients with GD. Furthermore, patients with GD showed a decrease in intestinal microbial diversity. Therefore, it indicates that the diversity of microbial strains is significantly reduced in GD patients, and patients with GD will undergo significant changes in intestinal microbiota, by comparing the intestinal flora of GD and healthy controls. These conclusions are expected to provide a preliminary reference for further researches on the interaction mechanism between intestinal flora and GD.

The macrophage heterogeneity: difference between mouse peritoneal exudate and splenic F4/80+ macrophages.

Macrophages isolated from various tissues manifest differences in cell shape, the expression of surface markers, as well as metabolic and functional activities. However, the heterogeneity of macrophages expressing the same marker in different tissues has not been fully addressed. In the present study, mouse F4/80+ peritoneal exudate macrophages (PEMs) and splenic macrophages (SPMs) appeared similar in most respects. But the percentages of cells expressing CD80, CD40, MHC-II, TLR2, or TLR4, but not CD11c, CD54, or CD23, in freshly isolated F4/80+ SPMs were significantly higher than those in PEMs, whereas the levels of CD86+ cells in F4/80+ SPMs were markedly lower than those in PEMs. After lipopolysaccharide (LPS) stimulation, F4/80+ SPMs expressed significantly higher levels of CD86, CD40, or MHC-II than F4/80+ PEMs, but not CD11c, CD80, CD54, or CD23. F4/80+ SPMs had remarkably lower non-opsonic phagocytotic capacity against chicken RBCs or allo-T cells than PEMs as determined by two-photon microscopes and flow cytometry. SPMs produced markedly more NO than PEMs when cultured with LPS or allo-T cells. Furthermore, SPMs exhibited stronger immunogenicity than PEMs, as determined by the ability to stimulate T cell proliferation, delayed type hypersensitivity, and IFN-gamma production. The data showed the differences between SPMs and PEMs with regard to the phenotypes, phagocytosis, and immunogenicity, which may offer important information for us to better understand the distinguished immune responses of macrophages in spleens and the peritoneal cavity.

Transforming growth factor-beta: an important role in CD4+CD25+ regulatory T cells and immune tolerance.

The transforming growth factor-beta (TGF-beta) protein family is highly evolutionarily conserved and they have been implicated in many biological processes. Also, TGF-beta can exert pivotal functions in the immune system. It is widely accepted that regulatory T cells (Treg cells) play an important role in the maintenance of the immune homeostasis, but the underlying molecular mechanisms through which they can gain and/or perform suppressive functions in an active way remains to be defined. Though the engagement of TGF-beta in the Treg cells has been discounted for a period of time, an emerging body of data has established a close link between Treg cells and TGF-beta, as TGF-beta has been demonstrated to induce the expression of Foxp3, which acts as a master regulator for the development and function of Treg cells. We will, herein, focus on the crucial role of TGF-beta signaling in Treg cell biology and summarize the current studies regarding TGF-beta in the generation and function of CD4+CD25+Treg cells both in vivo and in vitro.

BTLA, a new inhibitory B7 family receptor with a TNFR family ligand.

B and T lymphocyte attenuator (BTLA), identified as an immune inhibitory receptor recently, plays widespread roles on T and B cells. Emerging evidence has generated plentiful information on the mechanisms which BTLA mediates negative regulation in immune responses and involves in a variety of physiological and pathological processes. The exploration of the biological mechanisms and regulation of BTLA will open possibilities on novel therapeutic strategies in immune-related diseases.