Inova Diagnostics, a worldwide leader in autoimmune diagnostic reagents and systems for the clinical laboratory, is pleased to announce the US Food and Drug Administration clearance of QUANTA Lite Calprotectin Extended Range, an assay which aids in the diagnosis of Inflammatory Bowel Disease (IBD), and can help differentiate IBD from Irritable Bowel Syndrome (IBS).
The mammalian gastrointestinal tract hosts a diverse community of microbes including bacteria, fungi, protozoa, helminths, and viruses. Through coevolution, mammals and these microbes have developed a symbiosis that is sustained through the host’s continuous sensing of microbial factors and the generation of a tolerant or pro-inflammatory response. While analyzing T cell–driven colitis in nonlittermate mouse strains, we serendipitously identified that a nongenetic transmissible factor dramatically increased disease susceptibility. We identified the protozoan Tritrichomonas muris as the disease-exacerbating element. Furthermore, experimental colonization with T. muris induced an elevated Th1 response in the cecum of naive wild-type mice and accelerated colitis in Rag1 −/− mice after T cell transfer. Overall, we describe a novel cross-kingdom interaction within the murine gut that alters immune cell homeostasis and disease susceptibility. This example of unpredicted microbial priming of the immune response highlights the importance of studying trans-kingdom interactions and serves as a stark reminder of the importance of using littermate controls in all mouse research.
Matthew A. Odenwald & Jerrold R. Turner AffiliationsContributionsCorresponding author Nature Reviews Gastroenterology & Hepatology (2016) doi:10.1038/nrgastro.2016.169 Published online 16 November 2016
A fundamental function of the intestinal epithelium is to act as a barrier that limits interactions between luminal contents such as the intestinal microbiota, the underlying immune system and the remainder of the body, while supporting vectorial transport of nutrients, water and waste products. Epithelial barrier function requires a contiguous layer of cells as well as the junctions that seal the paracellular space between epithelial cells. Compromised intestinal barrier function has been associated with a number of disease states, both intestinal and systemic. Unfortunately, most current clinical data are correlative, making it difficult to separate cause from effect in interpreting the importance of barrier loss. Some data from experimental animal models suggest that compromised epithelial integrity might have a pathogenic role in specific gastrointestinal diseases, but no FDA-approved agents that target the epithelial barrier are presently available. To develop such therapies, a deeper understanding of both disease pathogenesis and mechanisms of barrier regulation must be reached. Here, we review and discuss mechanisms of intestinal barrier loss and the role of intestinal epithelial barrier function in pathogenesis of both intestinal and systemic diseases. We conclude with a discussion of potential strategies to restore the epithelial barrier.
With $15.5 million more in the bank, San Francisco startup uBiome is on a mission to scale and diversify its consumer gut bacteria tests into clinically actionable diagnostics.
CD8+ tissue-resident memory T cells (TRM cells) reside permanently in nonlymphoid tissues and provide a first line of protection against invading pathogens. However, the precise localization of CD8+ TRM cells in the lung, which physiologically consists of a markedly scant interstitium compared with other mucosa, remains unclear. In this study, we show that lung CD8+ TRM cells localize predominantly in specific niches created at the site of regeneration after tissue injury, whereas peripheral tissue-circulating CD8+ effector memory T cells (TEM cells) are widely but sparsely distributed in unaffected areas. Although CD69 inhibited sphingosine 1–phosphate receptor 1–mediated egress of CD8+ T cells immediately after their recruitment into lung tissues, such inhibition was not required for the retention of cells in the TRM niches. Furthermore, despite rigid segregation of TEM cells from the TRM niche, prime-pull strategy with cognate antigen enabled the conversion from TEM cells to TRM cells by creating de novo TRM niches. Such damage site–specific localization of CD8+ TRM cells may be important for efficient protection against secondary infections by respiratory pathogens.
We have known for over 60 years that smoking tobacco is one of the most avoidable risk factors for cancer. Yet the detailed mechanisms by which tobacco smoke damages the genome and creates the mutations that ultimately cause cancer are still not fully understood. Alexandrov et al. examined mutational signatures and DNA methylation changes in over 5000 genome sequences from 17 different cancer types linked to smoking (see the Perspective by Pfeifer). They found a complex pattern of mutational signatures. Only cancers originating in tissues directly exposed to smoke showed a signature characteristic of the known tobacco carcinogen benzo[ a ]pyrene. One mysterious signature was shared by all smoking-associated cancers but is of unknown origin. Smoking had only a modest effect on DNA methylation.
Science , this issue p. [618][1]; see also p. [549][2]
Mucosal Immunology is the official publication of the Society of Mucosal Immunology (SMI). It aims to provide a forum for both basic and clinical scientists to discuss all aspects of immunity and inflammation involving mucosal tissues.
Suppressor of cytokine signaling 1 (SOCS1) is a negative feedback inhibitor of cytoplasmic Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling. SOCS1 also contains a nuclear localization sequence (NLS), yet the in vivo importance of nuclear translocation is unknown. We generated transgenic mice containing mutated Socs1ΔNLS that fails to translocate in the cell nucleus (MGLtg mice). Whereas mice fully deficient for SOCS1 die within the first three weeks due to excessive interferon signaling and multiorgan inflammation, mice expressing only non-nuclear Socs1ΔNLS (Socs1-/-MGLtg mice) were rescued from early lethality. Canonical interferon gamma signaling was still functional in Socs1-/-MGLtg mice as shown by unaltered tyrosine phosphorylation of STAT1 and whole genome expression analysis. However, a subset of NFB inducible genes was dysregulated. Socs1-/-MGLtg mice spontaneously developed low-grade inflammation in the lung and had elevated Th2-type cytokines. Upon ovalbumin sensitization and challenge, airway eosinophilia was increased in Socs1-/-MGLtg mice. Decreased transepithelial electrical resistance (TER) in trachea epithelial cells from Socs1-/-MGLtg mice suggests disrupted epithelial cell barrier. The results indicate that nuclear SOCS1 is a regulator of local immunity in the lung and unravel a so far unrecognized function for SOCS1 in the cell nucleus.
Nature Immunology is a multidisciplinary journal that publishes papers of the highest quality and significance in all areas of immunology. Priority is given to work that provides fundamental insight into the workings of the immune system. Areas covered include, but are not limited to, innate immunity and inflammation; development; immune receptors, signaling and apoptosis; antigen presentation; gene regulation and recombination; cellular and systemic immunity; vaccines; immune tolerance; autoimmunity and tumor immunology, microbial immunopathology; and transplantation.
Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate.
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