Secondary lymphoid organs are important locations for the initiation of adaptive immune responses. They develop before birth, and their formation requires interaction between lymphotoxin-α₁s₂-expressing lymphoid-tissue inducer cells and lymphotoxin-s receptor-expressing stromal organizer cells. Here, we discuss new insights into the earliest phases of peripheral lymph node and Peyer's patch formation that occur before lymphotoxin-s receptor signalling and suggest a role for the developing nervous system. In addition, we discuss the differing requirements for the postnatal formation of mucosa-associated lymphoid tissues and tertiary lymphoid structures that develop at sites of chronic inflammation.

New insights into the development of lymphoid tissues.

https://www.hal.inserm.fr/inserm-00745108/document

Brain-gut interactions in inflammatory bowel disease.

Cytokine production is necessary to protect against pathogens and promote tissue repair, but excessive cytokine release can lead to systemic inflammation, organ failure and death Inflammatory responses are finely regulated to effectively guard from noxious stimuli The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways The effect of glucocorticoids and other humoral mediators on inflammatory responses has been studied extensively in the past decades In contrast, neural control of inflammation has only been recently described We summarize autonomic regulation of local and systemic inflammation through the 'cholinergic anti-inflammatory pathway', a mechanism consisting of the vagus nerve and its major neurotransmitter, acetylcholine, a process dependent on the nicotinic acetylcholine receptor alpha7 subunit We recapitulate additional sources of acetylcholine and their contribution to the inflammatory response, as well as acetylcholine regulation by acetylcholinesterase as a means to attenuate inflammation We discuss potential therapeutic applications to treat diseases characterized by acute or chronic inflammation, including autoimmune diseases, and propose future research directions

/pdf/cholinergic-control-of-inflammation-571iqnpp2f.pdf

Cholinergic control of inflammation.

The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts.

https://www.physiology.org/doi/pdf/10.1152/ajpgi.00048.2015

Homeostasis of the Gut Barrier and Potential Biomarkers.

Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS)

The cholinergic nervous system attenuates the production of pro-inflammatory cytokines and inhibits inflammatory processes. Hence, in animal models of intestinal inflammation, such as postoperative ileus and dextran sulfate sodium-induced colitis, vagus nerve stimulation ameliorates disease activity. On the other hand, in infectious models of microbial peritonitis, vagus nerve activation seemingly acts counteractive; it impairs bacterial clearance and increases mortality. It is originally indicated that the key mediator of the cholinergic anti-inflammatory pathway, acetylcholine (ACh), inhibits cytokine release directly via the alpha7 nicotinic ACh receptor (nAChR) expressed on macrophages. However, more recent data also point towards the vagus nerve as an indirect modulator of innate inflammatory processes, exerting its anti-inflammatory effects via postganglionic modulation of immune cells in primary immune organs. This review discusses advances in the possible mechanisms by which the vagus nerve can mediate the immune response, and the role of nAChR activation and signalling on macrophages and other immune cells.

The vagus nerve as a modulator of intestinal inflammation

/pdf/stimulation-of-the-vagus-nerve-attenuates-macrophage-2uj9kd30pk.pdf

E. P. van der Zanden

Papers

The vagus nerve as a modulator of intestinal inflammation

Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway (vol 6, pg 844, 2005)

The vagal anti-inflammatory pathway prevents postoperative ileus by nicotinic acetylcholine receptor activation on intestinal macrophages