NK cell subsets define sustained remission in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an immune-mediated, chronic inflammatory condition. With modern therapeutics and evidence-based management strategies, achieving sustained remission is increasingly common. To prevent complications associated with prolonged use of immunosuppressants, drug tapering or withdrawal is recommended.

Amelioration of Fibrotic Remodeling of Human 3-Dimensional Full-Thickness Skin by Transglutamase 2 Inhibition.

Objective: Fibrotic tissues are characterized by excessive crosslinking between extracellular matrix (ECM) proteins, rendering them more resistant to degradation. Although increased crosslinking of ECM is thought to play an important role for progression of tissue fibrosis, enhanced ECM crosslinking has not yet been targeted therapeutically in systemic sclerosis (SSc). Here, we investigated the role of transglutaminase 2 (TG2), a central crosslinking enzyme, in the activation of SSc fibroblasts.

Interleukin 17A and IL-17F Expression and Functional Responses in Rheumatoid Arthritis and Peripheral Spondyloarthritis.

Objective: Targeting the interleukin 17 (IL-17) axis is efficacious in psoriasis and spondyloarthritis (SpA), but not in rheumatoid arthritis (RA). We investigated potential differences in tissue expression and function of IL-17A and IL-17F in these conditions.

Methods: mRNA expression of cytokines and their receptors was assessed by quantitative PCR in psoriasis skin samples, in SpA and RA synovial tissue (ST) samples and in fibroblast-like synoviocytes (FLS).

Assessing the Mouse Intestinal Microbiota in Settings of Type-2 Immune Responses.

The microbial communities that reside within the mammalian host play important roles in the development of a robust host immune system. With the advent of sequencing technology and barcoding strategy of the bacterial 16S ribosomal RNA (rRNA) gene, microbiota studies are becoming more economical but also more important in many immunology studies. Here, we described a representative study protocol to characterize how the microbiota changes during an intestinal helminth infection, with emphasis on subtle aspects of the experimental design that are critical for data interpretation.

Rapid environmental effects on gut nematode susceptibility in rewilded mice.

Genetic and environmental factors shape host susceptibility to infection, but how and how rapidly environmental variation might alter the susceptibility of mammalian genotypes remains unknown. Here, we investigate the impacts of seminatural environments upon the nematode susceptibility profiles of inbred C57BL/6 mice. We hypothesized that natural exposure to microbes might directly (e.

Integrated Analysis of Biopsies from Inflammatory Bowel Disease Patients Identifies SAA1 as a Link Between Mucosal Microbes with TH17 and TH22 Cells.

Background: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD.

Methods: We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD.

Helminth infection promotes colonization resistance via type 2 immunity.

Increasing incidence of inflammatory bowel diseases, such as Crohn's disease, in developed nations is associated with changes to the microbial environment, such as decreased prevalence of helminth colonization and alterations to the gut microbiota. We find that helminth infection protects mice deficient in the Crohn's disease susceptibility gene Nod2 from intestinal abnormalities by inhibiting colonization by an inflammatory Bacteroides species. Resistance to Bacteroides colonization was dependent on type 2 immunity, which promoted the establishment of a protective microbiota enriched in Clostridiales.

Isolation and cytokine analysis of lamina propria lymphocytes from mucosal biopsies of the human colon.

Much of our understanding of gut-microbial interactions has come from mouse models. Intestinal immunity is complex and a combination of host genetics and environmental factors play a significant role in regulating intestinal immunity. Due to this complexity, no mouse model to date gives a complete and accurate representation of human intestinal diseases, such as inflammatory bowel diseases.

Heterogeneity across the murine small and large intestine.

The small and large intestine of the gastrointestinal tract (GIT) have evolved to have discrete functions with distinct anatomies and immune cell composition. The importance of these differences is underlined when considering that different pathogens have uniquely adapted to live in each region of the gut. Furthermore, different regions of the GIT are also associated with differences in susceptibility to diseases such as cancer and chronic inflammation.

Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus.

Nod2 has been extensively characterized as a bacterial sensor that induces an antimicrobial and inflammatory gene expression program. Therefore, it is unclear why Nod2 mutations that disrupt bacterial recognition are paradoxically among the highest risk factors for Crohn's disease, which involves an exaggerated immune response directed at intestinal bacteria. Here, we identified several abnormalities in the small-intestinal epithelium of Nod2(-/-) mice including inflammatory gene expression and goblet cell dysfunction, which were associated with excess interferon-γ production by intraepithelial lymphocytes and Myd88 activity.