Tag Archives: IL-22

The Dark Side of Retinoic Acid and Interleukin-22

Salmonella species growing on XLD agar - Showing H2S production
IL-22 secretion during intestinal inflammation gives Salmonella a competitive advantage.
This week on TIBDI: Th1 cells can activate macrophages with innate signals alone, retinoic acid is no hero in Crohn’s disease, and interleukin-22 allows some pathogens to thrive.

TCRs Are Not Always Needed

Macrophages and T cells play are important in inflammatory bowel disease (IBD). Learning about how these cells interact could lead to more insight about how IBD progresses. Hope O’Donnell of the University of Minnesota has now gleaned new insights about their interactions. She looked into the mechanisms behind non-cognate stimulation of Th1 cells (non-TCR stimulation) and their ability to secrete macrophage-activating IFNγ. Using genetically manipulated mice and a Salmonella infection model, her results show that Th1 (and CD8+) cells produce plenty of IFNγ as long as they are exposed to Toll-like receptor ligands and products of activated inflammasomes like interleukin (IL)-18 and IL-33. This study underscores the flexibility and strength of the adaptive immune response.

The Pitfalls of Retinoic Acid

Retinoic acid is the current darling of those studying anti-inflammatory responses as it has been shown that retinoic acid can lead to regulatory T cell development. To determine if retinoic acid was actually lowered during Crohn’s disease (CD), Dr. Theodore J. Sanders of the Blizard Institute in London measured retinaldehyde dehydrogenase (RALDH) activity in cell samples collected from CD patients and controls. In all of the dendritic cells and macrophages tested, the RALDH activity (ability to produce retinoic acid) was increased in CD patients compared to controls. Surprisingly, blocking retinoic acid signaling actually decreased the ability of monocytes to differentiate into TNFα-producing macrophages in in vitro tests. This would suggest that retinoic acid is less helpful in CD than what one would expect.

Salmonella Exploits Interleukin-22

Interleukin-22 is a cytokine that is designed to boost immune defenses at the gut-lumen interface. It induces antimicrobial peptide release along with factors that sequester essential metal ions (like iron) that bacteria need to grow. Dr. Judith Behnsen of the University of California has now discovered that these processes can be exploited by certain pathogens, like Salmonella. She found that IL-22 deficient mice were much less susceptible to Salmonella overgrowth. The reason was that Salmonella has the ability to compensate for the loss of ambient metal ions, while this is not the situation for many commensals. This allows Salmonella to create for a rather large niche for itself, while IL-22-induced processes decimate the competition.

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Bacterial Proteomics and Soluble CD83 Are Handy for IBD

2D-Gels
2D-gels can help decipher the bacterial proteome.
This week on TIBDI: Soluble CD83 may be a useful anti-inflammatory factor, bacterial proteomics reveals new Crohn’s disease biomarkers, and GATA3 is an important transcription factor for group 3 innate lymphoid cells.

Soluble CD83, the Anti-Inflammatory Molecule

In order to control signals of membrane-bound receptors, the body often employs soluble versions that act as ligand sponges, preventing signaling on the stationary, active molecule. This is also the case with the pro-inflammatory, co-stimulatory molecule CD83, which is expressed on activated dendritic cells as well as activated T and B cells. The researcher Jenny Eckhardt, located at the University Hospital Erlangen in Erlangen, Germany, realized that this process might be involved in controlling intestinal inflammation and sought more answers with her team. They found that administration of soluble CD83 prevented colitis in a mouse model of inflammatory bowel disease. This was associated with improvements in many inflammatory mediators. They also determined that the positive effects of soluble CD83 were induced by indoleamine 2,3-dioxygenase, which is known to have immunosuppressive properties.

Metaproteomics for Crohn’s Disease Monitoring

Catherine Juste of the French National Institute for Agricultural Research (INRA) has zeroed in on new molecular parameters for Crohn’s disease (CD), which may impact future diagnosis, monitoring and treatment. While many have focused on categorizing the intestinal microbiota signatures of CD patients, her team went one step further and looked at the microbial protein signature. They found that many proteins from Bacteroides species were over represented. Many of the over-expressed proteins were for the invasion and breaching of the mucosa. This unique method of looking at bacterial proteins could lead to new targets to help treat CD.

GATA3’s New Identity

GATA3 is a transcription factor most well known for its role in inducing T cell differentiation towards Th2. However, Nicolas Serafini of the Pasteur Institute and French Institute of Health and Medical Research (INSERM) has now found that GATA3 has many more uses including the induction of group 3 innate lymphoid cells (ILC3). ILC3 are essential for generating a wave of epithelial cell-activating IL-22 after intestinal bacteria infection. ILC3 are also characterized by the expression of the Th17-associated transcription factor RORγt. GATA3 was necessary for these cells during development, and their loss led to a reduced resistance against an intestinal bacterial pathogen.

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