Microbiota-derived butyrate restricts tuft cell differentiation via histone deacetylase 3 to modulate intestinal type 2 immunity.

Tuft cells in mucosal tissues are key regulators of type 2 immunity. Here, we examined the impact of the microbiota on tuft cell biology in the intestine. Succinate induction of tuft cells and type 2 innate lymphoid cells was elevated with loss of gut microbiota.

Dietary phytate primes epithelial antibacterial immunity in the intestine.

Although diet has long been associated with susceptibility to infection, the dietary components that regulate host defense remain poorly understood. Here, we demonstrate that consuming rice bran decreases susceptibility to intestinal infection with , a murine pathogen that is similar to enteropathogenic infection in humans. Rice bran naturally contains high levels of the substance phytate.

Neonatal microbiota-epithelial interactions that impact infection.

Despite modern therapeutic developments and prophylactic use of antibiotics during birth or in the first few months of life, enteric infections continue to be a major cause of neonatal mortality and morbidity globally. The neonatal period is characterized by initial intestinal colonization with microbiota and concurrent immune system development. It is also a sensitive window during which perturbations to the environment or host can significantly impact colonization by commensal microbes.

Commensal segmented filamentous bacteria-derived retinoic acid primes host defense to intestinal infection.

Interactions between the microbiota and mammalian host are essential for defense against infection, but the microbial-derived cues that mediate this relationship remain unclear. Here, we find that intestinal epithelial cell (IEC)-associated commensal bacteria, segmented filamentous bacteria (SFB), promote early protection against the pathogen Citrobacter rodentium, independent of CD4 T cells. SFB induced histone modifications in IECs at sites enriched for retinoic acid receptor motifs, suggesting that SFB may enhance defense through retinoic acid (RA).

Inflammation-Associated Microbiota Composition Across Domestic Animals.

Domestic animals represent important resources for understanding shared mechanisms underlying complex natural diseases that arise due to both genetic and environmental factors. Intestinal inflammation, particularly inflammatory bowel disease (IBD), is a significant health challenge in humans and domestic animals. While the etiology of IBD is multifactorial, imbalance of symbiotic gut microbiota has been hypothesized to play a central role in disease pathophysiology.

Microbiota-derived metabolite promotes HDAC3 activity in the gut.

The coevolution of mammalian hosts and their beneficial commensal microbes has led to development of symbiotic host-microbiota relationships. Epigenetic machinery permits mammalian cells to integrate environmental signals; however, how these pathways are fine-tuned by diverse cues from commensal bacteria is not well understood. Here we reveal a highly selective pathway through which microbiota-derived inositol phosphate regulates histone deacetylase 3 (HDAC3) activity in the intestine.

RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells.

Langerhans cells (LC) are the prototype langerin-expressing dendritic cells (DC) that reside specifically in the epidermis, but langerin-expressing conventional DCs also reside in the dermis and other tissues, yet the factors that regulate their development are unclear. Because retinoic acid receptor alpha (RARα) is highly expressed by LCs, we investigate the functions of RARα and retinoic acid (RA) in regulating the langerin-expressing DCs. Here we show that the development of LCs from embryonic and bone marrow-derived progenitors and langerinconventional DCs is profoundly regulated by the RARα-RA axis.

Succinylated chitosan derivative has local protective effects on intestinal inflammation.

We have previously reported on the anti-inflammatory effects of a water-soluble chitosan derivative, zwitterionic chitosan (ZWC). In the present study, we hypothesized that orally-administered ZWC would provide local anti-inflammatory effects in the intestinal lumen. ZWC indeed showed anti-inflammatory effects in various models including peritoneal macrophages, engineered THP1 monocytes, and Caco-2 cells.

Migration and Tissue Tropism of Innate Lymphoid Cells.

Innate lymphoid cell (ILCs) subsets differentially populate various barrier and non-barrier tissues, where they play important roles in tissue homeostasis and tissue-specific responses to pathogen attack. Recent findings have provided insight into the molecular mechanisms that guide ILC migration into peripheral tissues, revealing common features among different ILC subsets as well as important distinctions. Recent studies have also highlighted the impact of tissue-specific cues on ILC migration, and the importance of the local immunological milieu.

Human Tfh and Tfr cells: identification and assessment of their migration potential.

The ability of follicular T cells to migrate into B-cell follicles is central for them to participate in germinal center responses. The chemokine receptor CXCR5 is expressed by both Tfh and Tfr cells and is the defining marker for follicular T cells. In addition, Tfh and Tfr cells express additional chemokine receptors to enable them to interact with B cells and other cell types.