Airway basal stem cells are necessary for the maintenance of functional intraepithelial airway macrophages.

Stem cells are known to provide signals that contribute to the maintenance and function of neighboring cells. We demonstrate that Notch signaling arising from airway basal stem cells is necessary for the function of a unique population of intraepithelial airway macrophages (IAMs) in the murine trachea. Without this stem cell signaling, IAMs lose MHC II expression, which in turn prevents antigen-induced allergic inflammation.

Airway macrophage glycolysis controls lung homeostasis and responses to aeroallergen.

The lungs represent a dynamic microenvironment where airway macrophages (AMs) are the major lung-resident macrophages. AMs dictate the balance between tissue homeostasis and immune activation and thus have contradictory functions by maintaining tolerance and tissue homeostasis, as well as initiating strong inflammatory responses. Emerging evidence has highlighted the connection between macrophage function and cellular metabolism.

Airway basal stem cells are necessary for the maintenance of functional intraepithelial airway macrophages.

Adult stem cells play a crucial role in tissue homeostasis and repair through multiple mechanisms. In addition to being able to replace aged or damaged cells, stem cells provide signals that contribute to the maintenance and function of neighboring cells. In the lung, airway basal stem cells also produce cytokines and chemokines in response to inhaled irritants, allergens, and pathogens, which affect specific immune cell populations and shape the nature of the immune response.

Comprehensive characterization of ureagenesis in the spf mouse, a model of human ornithine transcarbamylase deficiency, reveals age-dependency of ammonia detoxification.

The most common ureagenesis defect is X-linked ornithine transcarbamylase (OTC) deficiency which is a main target for novel therapeutic interventions. The spf mouse model carries a variant (c.386G>A, p.

CARMA3 Mediates Allergic Lung Inflammation in Response to Alternaria alternata.

The airway epithelial cell (AEC) response to allergens helps initiate and propagate allergic inflammation in asthma. CARMA3 is a scaffold protein that mediates G protein-coupled receptor-induced NF-κB activation in airway epithelium. In this study, we demonstrate that mice with CARMA3-deficient AECs have reduced airway inflammation, as well as reduced type 2 cytokine levels in response to Alternaria alternata.

CARMA3 Is Critical for the Initiation of Allergic Airway Inflammation.

Innate immune responses to allergens by airway epithelial cells (AECs) help initiate and propagate the adaptive immune response associated with allergic airway inflammation in asthma. Activation of the transcription factor NF-κB in AECs by allergens or secondary mediators via G protein-coupled receptors (GPCRs) is an important component of this multifaceted inflammatory cascade. Members of the caspase recruitment domain family of proteins display tissue-specific expression and help mediate NF-κB activity in response to numerous stimuli.

Compartmentalized chemokine-dependent regulatory T-cell inhibition of allergic pulmonary inflammation.

Background: Induction of endogenous regulatory T (Treg) cells represents an exciting new potential modality for treating allergic diseases, such as asthma. Treg cells have been implicated in the regulation of asthma, but the anatomic location in which they exert their regulatory function and the mechanisms controlling the migration necessary for their suppressive function in asthma are not known. Understanding these aspects of Treg cell biology will be important for harnessing their power in the clinic.

Activin A and TGF-β promote T(H)9 cell-mediated pulmonary allergic pathology.

Background: IL-9-secreting (T(H)9) T cells are thought to represent a distinct T-cell subset. However, evidence for their functionality in disease is uncertain.

Objective: To define a functional phenotype for T(H)9-driven pathology in vivo.