RAG suppresses group 2 innate lymphoid cells.

Antigen specificity is the central trait distinguishing adaptive from innate immune function. Assembly of antigen-specific T cell and B cell receptors occurs through V(D)J recombination mediated by the Recombinase Activating Gene endonucleases RAG1 and RAG2 (collectively called RAG). In the absence of RAG, mature T and B cells do not develop and thus RAG is critically associated with adaptive immune function.

IL-33 potentiates histaminergic itch.

Background: Itch is a common symptom that can greatly diminish quality of life. Histamine is a potent endogenous pruritogen, and while antihistamines are often the first-line treatment for itch, in conditions like chronic spontaneous urticaria (CSU), many patients remain symptomatic while receiving maximal doses. Mechanisms that drive resistance to antihistamines are poorly defined.

Difelikefalin suppresses itch and reduces scratching independent of inflammation in a murine model of atopic dermatitis.

Background: Therapies specifically targeting nonhistaminergic pruritus are largely lacking. Difelikefalin (DFK) has been found to reduce itch in various chronic pruritic conditions, including atopic dermatitis (AD).

Objective: We sought to investigate the ability of DFK to impact scratching behavior, inflammatory mediators, and neuronal signaling in a murine model of AD.

A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain.

Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood.

IL-33 signaling in sensory neurons promotes dry skin itch.

Background: Chronic pruritus, or itch, is common and debilitating, but the neuroimmune mechanisms that drive chronic itch are only starting to be elucidated. Recent studies demonstrate that the IL-33 receptor (IL-33R) is expressed by sensory neurons. However, whether sensory neuron-restricted activity of IL-33 is necessary for chronic itch remains poorly understood.

is enriched in Crohn's disease intestinal tissue and impairs healing in mice.

Alterations of the mycobiota composition associated with Crohn's disease (CD) are challenging to link to defining elements of pathophysiology, such as poor injury repair. Using culture-dependent and -independent methods, we discovered that preferentially localized to and was abundant within incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD human subjects. cultures from injured mice and inflamed CD tissues impaired colonic healing when introduced into injured conventionally raised or gnotobiotic mice.

Immunosensation: Neuroimmune Cross Talk in the Skin.

Classically, skin was considered a mere structural barrier protecting organisms from a diversity of environmental insults. In recent decades, the cutaneous immune system has become recognized as a complex immunologic barrier involved in both antimicrobial immunity and homeostatic processes like wound healing. To sense a variety of chemical, mechanical, and thermal stimuli, the skin harbors one of the most sophisticated sensory networks in the body.

A basophil-neuronal axis promotes itch.

Itch is an evolutionarily conserved sensation that facilitates expulsion of pathogens and noxious stimuli from the skin. However, in organ failure, cancer, and chronic inflammatory disorders such as atopic dermatitis (AD), itch becomes chronic, intractable, and debilitating. In addition to chronic itch, patients often experience intense acute itch exacerbations.

New and emerging treatments for inflammatory itch.

Objective: To summarize recent therapeutic developments for chronic pruritus with a focus on allergic and type 2 inflammatory pathways.

Data Sources: Literature search of PubMed, industry websites, and review of the ClinicalTrials.gov database.

Long-Term Culture Captures Injury-Repair Cycles of Colonic Stem Cells.

The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hopx colitis-associated regenerative stem cell (CARSC) population that functionally contributes to mucosal repair in mouse models of colitis.

The Human Microbiota and Asthma.

Over the last few decades, advances in our understanding of microbial ecology have allowed us to appreciate the important role of microbial communities in maintaining human health. While much of this research has focused on gut microbes, microbial communities in other body sites and from the environment are increasingly recognized in human disease. Here, we discuss recent advances in our understanding of host-microbiota interactions in the development and manifestation of asthma focusing on three distinct microbial compartments.

Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease.

Graft-versus-host disease (GVHD) in the gastrointestinal (GI) tract remains the major cause of morbidity and nonrelapse mortality after BM transplantation (BMT). The Paneth cell protein regenerating islet-derived 3α (REG3α) is a biomarker specific for GI GVHD. REG3α serum levels rose in the systematic circulation as GVHD progressively destroyed Paneth cells and reduced GI epithelial barrier function.

Omenn Syndrome Presenting with Striking Erythroderma and Extreme Lymphocytosis in a Newborn.

Omenn syndrome is an autosomal recessive form of "leaky" severe combined immune deficiency resulting in distinct phenotypic features. The patient described herein had an atypical presentation of Omenn syndrome, with conspicuous erythroderma and extreme lymphocytosis at birth, in contrast to the typical evolution of rash seen during the first few weeks of life. In addition, the skin findings were secondary to infiltration of CD8 (cytotoxic) T-cells in contrast to the CD4 (helper) T-cells typically seen, which broadens the Omenn syndrome phenotype.

Crystal structure of a complex of NOD1 CARD and ubiquitin.

The Caspase Recruitment Domain (CARD) from the innate immune receptor NOD1 was crystallized with Ubiquitin (Ub). NOD1 CARD was present as a helix-swapped homodimer similar to other structures of NOD1 CARD, and Ub monomers formed a homodimer similar in conformation to Lys48-linked di-Ub. The interaction between NOD1 CARD and Ub in the crystal was mediated by novel binding sites on each molecule.

Ubiquitin regulates caspase recruitment domain-mediated signaling by nucleotide-binding oligomerization domain-containing proteins NOD1 and NOD2.

NOD1 and NOD2 (nucleotide-binding oligomerization domain-containing proteins) are intracellular pattern recognition receptors that activate inflammation and autophagy. These pathways rely on the caspase recruitment domains (CARDs) within the receptors, which serve as protein interaction platforms that coordinately regulate immune signaling. We show that NOD1 CARD binds ubiquitin (Ub), in addition to directly binding its downstream targets receptor-interacting protein kinase 2 (RIP2) and autophagy-related protein 16-1 (ATG16L1).