Mucosal Immunity

Depletion of the molecule gluconate halts gut colonization by a pathogen.

Oral tolerance is the process by which feeding of soluble proteins induces antigen-specific systemic immune unresponsiveness. Oral tolerance is thought to have a central role in suppressing immune responses to ‘harmless’ food antigens, and its failure can lead to development of pathologies such as food allergies or coeliac disease. However, on the basis of long-standing experimental observations, the relevance of oral tolerance in human health has achieved new prominence recently following the discovery that oral administration of peanut proteins prevents the development of peanut allergy in at-risk human infants. In this Review, we summarize the new mechanistic insights into three key processes necessary for the induction of tolerance to oral antigens: antigen uptake and transport across the small intestinal epithelial barrier to the underlying immune cells; the processing, transport and presentation of fed antigen by different populations of antigen-presenting cells; and the development of immunosuppressive T cell populations that mediate antigen-specific tolerance. In addition, we consider how related but distinct processes maintain tolerance to bacterial antigens in the large intestine. Finally, we outline the molecular mechanisms and functional consequences of failure of oral tolerance and how these may be modulated to enhance clinical outcomes and prevent disease. Oral tolerance describes how the oral administration of harmless antigens (such as dietary proteins) leads to systemic immune unresponsiveness to these antigens. Its failure can lead to conditions such as food allergies. This Review from Cerovic, Pabst and Mowat explores new insights into the mechanisms of oral tolerance, discussing how ingested antigens enter and are processed in the intestine, the roles for unique antigen-presenting cells and the induction of immunosuppressive T cell populations. The authors also examine the maintenance of tolerance to bacterial antigens in the intestine, and they discuss the mechanisms behind the failure of oral tolerance and potential clinical interventions.

Summary. The female reproductive tract accommodates and balances the unique immunological challenges of protection from sexually transmitted pathogens and

T cells are critical mediators of host health, protecting us from a variety of dangers. As such, they are responders to bacterial and viral infections, the

Fibroblasts are present throughout the body and function to maintain tissue homeostasis. Recent studies have identified diverse fibroblast subsets in healthy and injured tissues1,2, but the origins and functional roles of injury-induced fibroblast lineages remain unclear. Here we show that lung-specialized alveolar fibroblasts take on multiple molecular states with distinct roles in facilitating responses to fibrotic lung injury. We generate a genetic tool that uniquely targets alveolar fibroblasts to demonstrate their role in providing niches for alveolar stem cells in homeostasis and show that loss of this niche leads to exaggerated responses to acute lung injury. Lineage tracing identifies alveolar fibroblasts as the dominant origin for multiple emergent fibroblast subsets sequentially driven by inflammatory and pro-fibrotic signals after injury. We identify similar, but not completely identical, fibroblast lineages in human pulmonary fibrosis. TGFβ negatively regulates an inflammatory fibroblast subset that emerges early after injury and stimulates the differentiation into fibrotic fibroblasts to elicit intra-alveolar fibrosis. Blocking the induction of fibrotic fibroblasts in the alveolar fibroblast lineage abrogates fibrosis but exacerbates lung inflammation. These results demonstrate the multifaceted roles of the alveolar fibroblast lineage in maintaining normal alveolar homeostasis and orchestrating sequential responses to lung injury. In mouse and human, lung-specialized alveolar fibroblasts adopt multiple molecular states that are induced by pro-inflammatory and fibrotic signals and have diverse protective roles against lung injury.

Drooling into a tube is not only more comfortable than nasal testing, it could also detect disease earlier.

The findings, published July 31 in Science Advances, provide further evidence that so-called mucosal vaccines sprayed into the nose or dropped into the mouth…

Vaccination stands out as one of the most revolutionary discoveries in medical science, benefiting not only humans but also extending its critical impact to many animal species including fish. This advancement plays a pivotal role in preventing diseases and ensuring the health and sustainability of

Written by Claire Kowalick A breakthrough for biomedical research promises new insight into immunotherapy development and disease modeling. Scientists at The University of Texas Health Science Center at San Antonio have created a humanized mouse model with a human immune system and a human-like gut microbiome that is capable of mounting specific antibody responses. The scientists […]