Metabolic requirements of type 2 lymphocytes in allergic disease.

Allergic diseases continue to increase in prevalence across the globe. Decades of research has uncovered the cytokines and transcription factors that are central to the allergic immune response, but only in the last few years have we begun to understand the metabolic requirements of allergic immunity. Here, we discuss the metabolic features of so-called 'type 2' lymphocytes, which are heavily implicated in allergy.

Single-cell RNA sequencing of cells from fresh or frozen tissue reveals a signature of freezing marked by heightened stress and activation.

Thawing of viably frozen human tissue T cells, ILCs, and NK cells and subsequent single-cell RNA sequencing reveals that recovery of cellular subclusters is variably impacted. While freeze-thawing does not alter the transcriptional profiles of cells, it upregulates genes and gene pathways associated with stress and activation.

Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity.

Immune cell dysfunction within the tumor microenvironment (TME) undermines the control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) cells; however, the temporal dynamics, mechanistic underpinning and functional significance of the NK cell compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of intratumoral NK cells.

The single-cell transcriptional landscape of innate and adaptive lymphocytes in pediatric-onset colitis.

Innate lymphoid cells (ILCs) are considered innate counterparts of adaptive T cells; however, their common and unique transcriptional signatures in pediatric inflammatory bowel disease (pIBD) are largely unknown. Here, we report a dysregulated colonic ILC composition in pIBD colitis that correlates with inflammatory activity, including accumulation of naive-like CD45RACD62L ILCs. Weighted gene co-expression network analysis (WGCNA) reveals modules of genes that are shared or unique across innate and adaptive lymphocytes.

Obese asthma phenotypes display distinct plasma biomarker profiles.

Background: Obese asthma is a complex phenotype and further characterization of the pathophysiology is needed. This study aimed to explore inflammation-related plasma biomarkers in lean and overweight/obese asthmatics.

Methods: We elucidated levels of inflammation-related plasma proteins in obese asthma phenotypes in the population-based cohort BAMSE (Swedish: Children, Allergy, Milieu, Stockholm, Epidemiology) using data from 2069 24-26-year-olds.

Recombinant multimeric dog allergen prevents airway hyperresponsiveness in a model of asthma marked by vigorous T 2 and T 17 cell responses.

Background: Allergy to dogs affects around 10% of the population in developed countries. Immune therapy of allergic patients with dog allergen extracts has shown limited therapeutic benefit.

Methods: We established a mouse model of dog allergy by repeatedly administering dog dander and epithelium extracts via the intranasal route.

The Role of PPAR-γ in Allergic Disease.

Purpose Of Review: The incidence of allergic diseases such as asthma, rhinitis and atopic dermatitis has risen at an alarming rate over the last century. Thus, there is a clear need to understand the critical factors that drive such pathologic immune responses. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that has emerged as an important regulator of multiple cell types involved in the inflammatory response to allergens; from airway epithelial cells to T Helper (TH) cells.

Single-cell analysis pinpoints distinct populations of cytotoxic CD4 T cells and an IL-10CD109 T2 cell population in nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a chronic inflammatory process often associated with comorbid asthma. In this study, we analyzed the transcriptomes of single T helper (T) cells from nasal polyps of patients with CRSwNP and validated these findings using multiparameter flow cytometry. Polyp tissue contained suppressive T regulatory (T) cells, T2 cells, type 2 innate lymphoid cells, and three transcriptionally distinct subsets of cytotoxic CD4 T cells (CD4 CTL).

GPR43 regulates marginal zone B-cell responses to foreign and endogenous antigens.

Marginal zone (MZ) B cells are innate-like B cells that produce polyreactive antibodies with an affinity for microbial molecular patterns and carbohydrate ligands. MZ B cells have been shown to be important in mediating immunity to various bacteria including Streptococcus pneumoniae and are also implicated in inflammatory syndromes including lupus erythematosus. The intestinal microbiota is responsible for producing short-chain fatty acids, which can regulate immune cell function by several mechanisms including ligation of the G-protein-coupled receptor (GPR)43.

PD-1 expression affects cytokine production by ILC2 and is influenced by peroxisome proliferator-activated receptor-γ.

Introduction: Innate lymphoid cells (ILCs) can provide early cytokine help against a variety of pathogens in the lungs and gastrointestinal tract. Type 2 ILC (ILC2) are comparable to T helper 2 cells found in the adaptive immune system, which secrete cytokines such as interleukin 5 (IL-5) and IL-13 and have been found to play roles in host defense against helminth infections and in allergic responses. Recent studies have identified that programmed cell death protein 1 (PD-1) and peroxisome proliferator activated receptor-γ (PPAR-γ) are highly expressed by ILC2.

The Metabolic Requirements of Th2 Cell Differentiation.

Upon activation, naïve CD4 T cells differentiate into a number of specialized T helper (Th) cell subsets. Th2 cells are central players in immunity to helminths and are implicated in mediating the inflammatory pathology associated with allergies. The differentiation of Th2 cells is dependent on transcription factors such as GATA3 and STAT6, which prime Th2 cells for the secretion of interleukin- (IL-) 4, IL-5, and IL-13.

Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells.

Naive CD4 T cells differentiate into functionally diverse T helper (Th) cell subsets. Th2 cells play a pathogenic role in asthma, yet a clear picture of their transcriptional profile is lacking. We performed single-cell RNA sequencing (scRNA-seq) of T helper cells from lymph node, lung, and airways in the house dust mite (HDM) model of allergic airway disease.

Multi-faceted inhibition of dendritic cell function by CD4Foxp3 regulatory T cells.

CTLA-4 is required for CD4Foxp3 regulatory T (Treg) cell function, but its mode of action remains incompletely defined. Herein we generated Ctla-4Foxp3-Cre mice with Treg cells exclusively expressing a naturally occurring, ligand-independent isoform of CTLA-4 (liCTLA-4) that cannot interact with the costimulatory molecules CD80 and CD86. The mice did not exhibit any signs of effector T cell activation early in life, however, at 6 months of age they exhibited excessive T cell activation and inflammation in lungs.

PPAR-γ promotes type 2 immune responses in allergy and nematode infection.

A hallmark of immunity to worm infections and many allergies is a strong type 2 immune response. This is characterized by the production of cytokines interleukin-5 (IL-5) and IL-13 by adaptive T helper 2 (T2) cells and/or type 2 innate lymphoid cells. Peroxisome proliferator activated receptor-γ (PPAR-γ) is typically regarded as an anti-inflammatory factor.

The choice of adjuvant determines the cytokine profile of T cells in proteoglycan-induced arthritis but does not influence disease severity.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic inflammation of the synovial joints. Collagen-induced arthritis (CIA) and proteoglycan-induced arthritis (PGIA) are mouse models of inflammatory arthritis; CIA is a T helper type 17 (Th17) -dependent disease that is induced with antigen in complete Freund's adjuvant, whereas PGIA is Th1-mediated and is induced using antigen in dimethyldioctadecyl-ammonium bromide (DDA) as an adjuvant. To investigate whether the type of adjuvant determines the cytokine profile of the pathogenic T cells, we have compared the effect of CFA and DDA on T-cell responses in a single arthritis model.