The yin and yang of B cells in a constant state of battle: intestinal inflammation and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, defined by a clinical relapse-remitting course. Affecting people worldwide, the origin of IBD is still undefined, arising as a consequence of the interaction between genes, environment, and microbiota. Although the root cause is difficult to identify, data clearly indicate that dysbiosis and pathogenic microbial taxa are connected with the establishment and clinical course of IBD. The composition of the microbiota is shaped by plasma cell IgA secretion and binding, while cytokines such as IL10 or IFN-γ are important fine-tuners of the immune response in the gastrointestinal environment. B cells may also influence the course of inflammation by promoting either an anti-inflammatory or a pro-inflammatory milieu. Here, we discuss IgA-producing B regulatory cells as an anti-inflammatory factor in intestinal inflammation. Moreover, we specify the context of IgA and IgG as players that can potentially participate in mucosal inflammation. Finally, we discuss the role of B cells in mouse infection models where IL10, IgA, or IgG contribute to the outcome of the infection.

Systemic desensitization through TRPA1 channels by capsazepine and mustard oil - a novel strategy against inflammation and pain.

We demonstrate a novel dual strategy against inflammation and pain through body-wide desensitization of nociceptors via TRPA1. Attenuation of experimental colitis by capsazepine (CPZ) has long been attributed to its antagonistic action on TRPV1 and associated inhibition of neurogenic inflammation. In contrast, we found that CPZ exerts its anti-inflammatory effects via profound desensitization of TRPA1. Micromolar CPZ induced calcium influx in isolated dorsal root ganglion (DRG) neurons from wild-type (WT) but not TRPA1-deficient mice. CPZ-induced calcium transients in human TRPA1-expressing HEK293t cells were blocked by the selective TRPA1 antagonists HC 030031 and A967079 and involved three cysteine residues in the N-terminal domain. Intriguingly, both colonic enemas and drinking water with CPZ led to profound systemic hypoalgesia in WT and TRPV1(-/-) but not TRPA1(-/-) mice. These findings may guide the development of a novel class of disease-modifying drugs with anti-inflammatory and anti-nociceptive effects.