TL1A/DR3 signaling regulates the generation of pathogenic Th9 cells in experimental inflammatory bowel disease.

Objective: Death receptor 3 (DR3) and its ligand tumor necrosis factor like ligand 1A (TL1A), are involved in the regulation of the balance between effector and regulatory T cells in IBD. New evidence suggests a role of IL-9-secreting Th9 cells in the pathogenesis of ulcerative colitis (UC), although the molecular pathways through which IL-9 and Th9 cells may mediate intestinal inflammation in Crohn's disease (CD) are still unclear.

Design: We investigated the role of DR3 signaling in the differentiation of Th9 cells in mouse models of CD-like ileitis and colitis, including SAMP1/YitFc (SAMP) mice.

Candida tropicalis Infection Modulates the Gut Microbiome and Confers Enhanced Susceptibility to Colitis in Mice.

Background & Aims: We previously showed that abundance of Candida tropicalis is significantly greater in Crohn's disease patients compared with first-degree relatives without Crohn's disease. The aim of this study was to determine the effects and mechanisms of action of C tropicalis infection on intestinal inflammation and injury in mice.

Methods: C57BL/6 mice were inoculated with C tropicalis, and colitis was induced by administration of dextran sodium sulfate in drinking water.

NOD2 drives early IL-33-dependent expansion of group 2 innate lymphoid cells during Crohn's disease-like ileitis.

Innate lymphoid cells (ILCs) are enriched at barrier surfaces, including the gastrointestinal tract. While most studies have focused on the balance between pathogenic group 1 ILCs (ILC1s) and protective ILC3s in maintaining gut homeostasis and during chronic intestinal inflammation, such as Crohn's disease (CD), less is known regarding ILC2s. Using an established murine model of CD-like ileitis, i.

Cytokine-Mediated Regulation of Innate Lymphoid Cell Plasticity in Gut Mucosal Immunity.

Mucosal barriers are active sites that encounter a bombardment of antigenic stimuli derived from both the commensal flora and a variety of pathogens, as well as from environmental insults. As such, the ability to mount appropriate innate immune responses is an important first line of defense that confers protection to the host. Central to innate immunity are innate lymphoid cells (ILCs), which were first described a decade ago, and represent a family of heterogeneous cells driven by specific transcription factors and exhibit distinct cytokine profiles that are shared with their CD4 T-helper cell counterparts.

Interleukin 33 Triggers Early Eosinophil-Dependent Events Leading to Metaplasia in a Chronic Model of Gastritis-Prone Mice.

Background & Aims: Interleukin (IL)33/IL1F11 is an important mediator for the development of type 2 T-helper cell (Th2)-driven inflammatory disorders and has also been implicated in the pathogenesis of gastrointestinal (GI)-related cancers, including gastric carcinoma. We therefore sought to mechanistically determine IL33's potential role as a critical factor linking chronic inflammation and gastric carcinogenesis using gastritis-prone SAMP1/YitFc (SAMP) mice.

Methods: SAMP and (parental control) AKR mice were assessed for baseline gastritis and progression to metaplasia.

Cross-talk between type 3 innate lymphoid cells and the gut microbiota in inflammatory bowel disease.

Purpose Of Review: Innate lymphoid cells (ILCs) are a newly-identified population of immune cells prevalent in, but not limited to, mucosal tissues that not only play a significant role in immune homeostasis and host defense, but also in disease pathogenesis. This review highlights the importance of type 3 ILCs (ILC3s) and their interactions with the intestinal microflora, both in maintaining gut health and in the development of inflammatory bowel disease (IBD).

Recent Findings: Distinct lineages of ILCs are defined based on the presence of cell surface proteins, secretion of effector cytokines and expression of master transcription factors that determine their differentiation and inflammatory behavior.

Cornea-infiltrating and lymph node dendritic cells contribute to CD4+ T cell expansion after herpes simplex virus-1 ocular infection.

After HSV type 1 corneal infection, CD4(+) T cells are expanded in the draining lymph nodes (DLNs) and restimulated in the infected cornea to regulate the destructive inflammatory disease herpes stromal keratitis (HSK). The contribution of cornea resident, cornea-infiltrating, and DLN resident dendritic cells (DC) to CD4(+) T cell expansion in DLNs and restimulation in corneas is unknown. Cornea resident and cornea-infiltrating DCs were selectively depleted by timed local (subconjunctival) injection of diphtheria toxin (DT) into mice that express high-affinity DT receptors from the CD11c promoter.

Antigen-presenting cells are stratified within normal human corneas and are rapidly mobilized during ex vivo viral infection.

Purpose: To define the phenotype and location of antigen-presenting cells (APCs) in normal donor human corneas, and to assess the response of APC to herpes simplex virus type 1 (HSV-1) infection.

Methods: Donor human corneal tissue was analyzed by fluorescence confocal microscopy and flow cytometry to determine the phenotype and location of tissue-resident APCs. Confocal fluorescence microscopy was also utilized to investigate the response of corneal resident APCs to ex vivo infection with HSV-1.

Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea.

Purpose: The secreted Ly6/uPAR-related protein-1 (Slurp1), associated with the hyperkeratotic disorder mal de Meleda, is abundantly expressed in corneas. Here, we examine its corneal expression and functions.

Methods: Gene expression was quantified by quantitative PCR (qPCR), immunoblots, and immunofluorescent staining.

Ethyl pyruvate ameliorates endotoxin-induced corneal inflammation.

Purpose: The purpose of this study was to evaluate the anti-inflammatory effect of ethyl pyruvate (EP) in a mouse model of lipopolysaccharide (LPS)-induced corneal inflammation.

Methods: LPS was injected intrastromally into the corneas of C57BL/6 mice followed by treatment with a solution of 2.5% EP in 0.

Early responding dendritic cells direct the local NK response to control herpes simplex virus 1 infection within the cornea.

Dendritic cells (DCs) regulate both innate and adaptive immune responses. In this article, we exploit the unique avascularity of the cornea to examine a role for local or very early infiltrating DCs in regulating the migration of blood-derived innate immune cells toward HSV-1 lesions. A single systemic diphtheria toxin treatment 2 d before HSV-1 corneal infection transiently depleted CD11c(+) DCs from both the cornea and lymphoid organs of CD11c-DTR bone marrow chimeric mice for up to 24 h postinfection.