The immune modifying effects of amino acids on gut-associated lymphoid tissue

The intestine and the gut-associated lymphoid tissue（GALT） are essential components of whole body immune defense,protecting the body from foreign antigens and pathogens,while allowing tolerance to commensal bacteria and dietary antigens.The requirement for protein to support the immune system is well established.Less is known regarding the immune modifying properties of individual amino acids,particularly on the GALT.Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake,but the availability of specific dietary amino acids（in particular glutamine,glutamate,and arginine,and perhaps methionine,cysteine and threonine） are essential to optimizing the immune functions of the intestine and the proximal resident immune cells.These amino acids each have unique properties that include,maintaining the integrity,growth and function of the intestine,as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers,specific T cell functions,and the secretion of IgA by lamina propria cells.Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters.Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.

Gut-associated lymphoid tissue or so-called “dome” carcinoma of the colon: Review

AIM To present a comprehensive review of the etiology, clinical features, macroscopic and pathological findings, and clinical significance of Gut-associated lymphoid tissue or "dome" carcinoma of the colon.METHODS The English language medical literature on gut-or gastrointestinal-associated lymphoid tissue(GALT) or "dome" carcinoma of the colon was searched and appraised.RESULTS GALT/dome-type carcinomas of the colon are thought to arise from the M-cells of the lymphoglandular complex of the intestine. They are typically asymptomatic and have a characteristic endoscopic plaque-or "dome"-like appearance. Although the histology of GALT/dome-type carcinomas displays some variability, they are characterized by submucosal localization, a prominent lymphoid infiltrate with germinal center formation, tumor-infiltrating lymphocytes, absence of desmoplasia, and dilated glands lined by columnar epithelial cells with bland nuclear features and cytoplasmic eosinophilia. None of the patients reported in the literature with follow-up have developed metastatic disease or local recurrence.CONCLUSION Increased awareness amongst histopathologists of this variant of colorectal adenocarcinoma is likely to lead to the recognition of more cases.

Carcinoma in gut-associated lymphoid tissue in ulcerative colitis: Case report and review of literature

The colorectal mucosa includes two quantitatively, structurally and functionally dissimilar areas: one, built with columnar and goblet cells, covers the vast majority of the mucosa, and the other consists of scattered minute gut-associated lymphoid tissue (GALT). The overwhelming majority of colorectal carcinomas evolve in GALT-free mucosal areas and very rarely in GALT aggregates. Remarkably, the colonic mucosa in patients with ulcerative colitis (UC) displays a high number of newly formed GALT-aggregates. The patient here described is a 68-year-old female with a history of UC since 1984. At surveillance colonoscopy in 2012, one of two detected polyps was a tubular adenoma with high-grade dysplasia. Beneath this adenoma, a well-circumscribed GALT sheltering a carcinoma was found. Serial sections revealed no connection between the villous adenomaand the GALT-carcinoma. The GALT-carcinoma here reported seems to have evolved in a newly formed, UC- dependent, GALT complex. This notion is substantiated by the fact that 27% or 4 out of the 15 cases of GALT- carcinomas in the colon reported in the literature (including the present case) evolved in patients with UC.

Isolation and specific detection of two major schistosoma gut-associated circulating antigens

Objectives To investigate the nature of the common epitopes of Schistosoma japonicum (S. japonicum) circulating anodic (CAA) and circulating cathodic antigen (CCA) and to try to obtain sufficient purified material to set up a standard series for quantitative determinations.Methods Isolation of the two worm fractions from a trichloroacetic acid (TCA) soluble preparation of S. japonicum adult worm antigen (AWAj-TCA) via Mono-Q anion exchange chromatography was performed and analysis of specific reactivity of the eluted fractions was done by antigen-capture Enzyme Linked Immuno Sorbent Assay (ELISA) specific for CAA or CCA with reference to affinity purified preparations of S. mansoni CAA and CCA. Results When an ionic strength gradient was used, CCA was eluted in two major peaks, an unbound fraction CCA-1, and a major bound fraction, CCA-2. Two additional minor peaks, CCA-3 and CCA-4, were eluted at higher ionic strengths. CAA was only detected in the bound fraction, partly overlapping with CCA-3. In the CCA-1 and CCA-2 fractions, reactivity was only found in the antigen-capture ELISA using anti-CCA McAbs both for capture and detection. The CAA fraction was predominantly found to be positive in the antigen-capture ELISA using anti-CAA McAbs both for capture and detection. However, in ELISA using combined anti-CCA and anti-CAA McAbs for capture and detection, this fraction showed some reactivity.Conclusion The two CCA fractions contain molecules which bear at least two CCA-epitopes; the CAA fraction contains molecules which contain at least two CAA-epitopes, and one CCA-epitope.

NKR-P1B expression in gut-associated innate lymphoid cells is required for the control of gastrointestinal tract infections

Helper-type innate lymphoid cells(ILC)play an important role in intestinal homeostasis.Members of the NKR-P1 gene family are expressed in various innate immune cells,including natural killer(NK)cells,and their cognate Clr ligand family members are expressed in various specialized tissues,including the intestinal epithelium,where they may play an important role in mucosalassociated innate immune responses.In this study,we show that the inhibitory NKR-P1B receptor,but not the Ly49 receptor,is expressed in gut-resident NK cells,ILC,and a subset ofγδT cells in a tissue-specific manner.ILC3 cells constitute the predominant cell subset expressing NKR-P1B in the gut lamina propria.The known NKR-P1B ligand Clr-b is broadly expressed in gut-associated cells of hematopoietic origin.The genetic deletion of NKR-P1B results in a higher frequency and number of ILC3 andγδT cells in the gut lamina propria.However,the function of gut-resident ILC3,NK,andγδT cells in NKR-P1B-deficient mice is impaired during gastrointestinal tract infection by Citrobacter rodentium or Salmonella typhimurium,resulting in increased systemic bacterial dissemination in NKR-P1B-deficient mice.Our findings highlight the role of the NKR-P1B:Clr-b recognition system in the modulation of intestinal innate immune cell functions.

IgA nephropathy associated with Crohn's disease

The relationship between IgA nephropathy(IgAN)and Crohn’s disease was reported.IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure,and up to 50%of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis.However,specific and effective therapeutic strategies are still lacking.In this review,we discuss the possibility of the mechanism involved in IgAN associated with Crohn’s disease based on the findings of basic and clinical studies.Although the etiology of IgAN associated with Crohn’s disease is not permanent and various factors are thought to be involved,the stabilization of the disease condition of Crohn’s disease is believed to help treat IgAN.

鸡嗉囊中淋巴细胞发育的研究

【目的】研究鸡出壳后不同日龄嗉囊中T淋巴细胞及其亚群和B淋巴细胞的定位分布及数量变化规律等一系列的发育过程．【方法】采用单克隆抗体，通过免疫组织化学方法，观察并统计各取材日龄相应细胞的分布和数量．【结果和结论】1日龄时， CD3＋、CD4＋和CD8＋细胞即已出现， Bu-1 b＋细胞于出壳后4日龄时出现．定位分布上， CD3＋细胞主要分布于黏膜上皮基底层及固有层中，7日龄首次出现以CD3＋细胞为中心的淋巴聚集物；CD4＋细胞主要分布于固有层中；CD8＋细胞最初主要分布在黏膜固有层中，随日龄增长逐渐向上皮方向突入，最终形成含有CD8＋细胞浸润的淋巴上皮；Bu-1b＋细胞主要分布于黏膜固有层中，特别是在小血管周围．于35日龄观察到以Bu-1b＋细胞为中心的生发中心．在数量变化上，CD3＋、CD4＋、CD8＋细胞数量整体呈逐渐增加趋势，部分阳性细胞数量在14和21日龄时稍有下降，35～56日龄时阳性细胞数量缓慢增加，基本达到成熟水平．Bu-1b＋细胞数量随着日龄的增加持续增多，且后期的增长速率大于T细胞的增长速率．结果表明，嗉囊作为鸡消化系统的一部分，具有由淋巴细胞和淋巴聚集物构成的免疫防线，为肠相关淋巴组织中的一个重要组成部分．

Driving Forces of AIDS Pathogenesis:Massive CD4^+ T Lymphocyte Depletion and Abnormal Immune Activation

The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the immune system. The infected host undergoes an asymptomatic period lasting several years with low viral load and ostensibly healthy status, which is presumably due to virus-specific adaptive immune responses. In the absence of therapy, an overwhelming majority of cases develop to AIDS within 8-10 years of latent infection. In this review, we discuss the roles in AIDS pathogenesis played by massive CD4+ T lymphocytes depletion in gut-associated lymphoid tissue (GALT) during acute infection and abnormal immune activation emerging in the later part of chronic phase.

Human activity over natural inputs determines the bacterial community in an ice core from the Muztag ata glacier

Ice core provides a valuable vertical timeline of past climates and anthropogenic activities.Environmental proxies have been widely used in these studies,but there are few biological indicators available.To address this gap,we investigated the bacterial community from a 74 m ice core of Muztag ata glacier on the Tibetan Plateau to link biological indicators with past climate and anthropogenic activities.By analyzing the portion of the ice core with environmental proxies available(corresponding to 1907 to 1991),we observed an increase in bacterial richness throughout the ice core,which was associated with higher NH_(4)^(+),an indicator of agricultural development.The bacterial community was jointly determined by human activity,natural input,and air temperature,with a strong human influence after the 1950s.Furthermore,the relative abundance of animal gut-associated bacteria,including Aerococcaceae,Nocardiaceae,Muribaculaceae,and Lachnospiraceae,was associated with livestock number changes in the Central Asian region.Together with other bacterial lineages,they jointly explained 59.8%of the livestock number changes.This study provides quantitative evidence of the associations between bacterial indicators and past climate and human activities,highlighting the potential of using bacterial proxies for ice core studies.

Antiosteoporotic Tetrahydroxanthone Dimers from Aspergillus brunneoviolaceus FB-2 Residing in Human Gut

A complex community of human-associated microorganisms plays diversely important roles in maintaining health,and the metabolites help to define whether a particular human-associated microbe is a friend or a foe.This work shows that Aspergillus brunneoviolaceus FB-2,derived from the stool of a healthy individual,produces a family of antiosteoporotic xanthone dinners including penibishexahydroxanthone A(1)and brunneoxanthones A-E(2-6,undescribed previously).The structures of 1-6 were elucidated by MS and NMR spectroscopic analysis,and the absolute configuration of 2 was established by X-ray crystallography.Compounds 4-6 are relatively rare examples of highly oxidized heterodimeric xanthones with an 8-ketone functionality.Finally,the prednisolone-induced osteoporotic zebrafish enabled our demonstration that the antiosteoporotic effects of 1-6 are dose-dependent.