Mechanisms and Functions of Inflammasomes

Research over the last 7 years has led to the formal identification of innate lymphoid cells (ILCs), increased the understanding of their tissue distribution and has established essential functions of ILCs in diverse physiological processes. These include resistance to pathogens, the regulation of autoimmune inflammation, tissue remodeling, cancer and metabolic homeostasis. Notably, many ILC functions appear to be regulated by mechanisms distinct from those of other innate and adaptive immune cells. In this Review, we focus on how group 2 ILC (ILC2) and group 3 ILC (ILC3) responses are regulated and how these cells interact with other immune and non-immune cells to mediate their functions. We highlight experimental evidence from mouse models and patient-based studies that have elucidated the effects of ILCs on the maintenance of tissue homeostasis and the consequences for health and disease.

Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis

Innate lymphoid cells (ILCs) are a growing family of immune cells that mirror the phenotypes and functions of T cells. However, in contrast to T cells, ILCs do not express acquired antigen receptors or undergo clonal selection and expansion when stimulated. Instead, ILCs react promptly to signals from infected or injured tissues and produce an array of secreted proteins termed cytokines that direct the developing immune response into one that is adapted to the original insult. The complex cross-talk between microenvironment, ILCs, and adaptive immunity remains to be fully deciphered. Only by understanding these complex regulatory networks can the power of ILCs be controlled or unleashed in order to regulate or enhance immune responses in disease prevention and therapy.

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Innate lymphoid cells: A new paradigm in immunology

Obesity is a vast public health problem and both a major risk factor and disease modifier for asthma in children and adults. Obese subjects have increased asthma risk, and obese asthmatic patients have more symptoms, more frequent and severe exacerbations, reduced response to several asthma medications, and decreased quality of life. Obese asthma is a complex syndrome, including different phenotypes of disease that are just beginning to be understood. We examine the epidemiology and characteristics of this syndrome in children and adults, as well as the changes in lung function seen in each age group. We then discuss the better recognized factors and mechanisms involved in disease pathogenesis, focusing particularly on diet and nutrients, the microbiome, inflammatory and metabolic dysregulation, and the genetics/genomics of obese asthma. Finally, we describe current evidence on the effect of weight loss and mention some important future directions for research in the field.

https://www.atsjournals.org/doi/pdf/10.1164/rccm.201203-0573OC

Obesity and asthma

A previously unappreciated cell type of the innate immune system, termed innate lymphoid cells (ILCs), has been characterized in mice and humans and found to influence the induction, regulation and resolution of inflammation. ILCs have an important role in these processes in mouse models of infection, inflammation and tissue repair. Further, disease-association studies in defined patient populations have identified significant alterations in ILC responses, suggesting a potential role for these cell populations in human health and disease. In this review we discuss the emerging family of ILCs, the role of ILCs in inflammation, and how current or novel therapeutic strategies could be used to selectively modulate ILC responses and limit chronic inflammatory diseases.

/pdf/innate-lymphoid-cells-in-the-initiation-regulation-and-42icn3j673.pdf

Innate lymphoid cells in the initiation, regulation and resolution of inflammation

The prevalence and severity of asthma has been linked to hypovitaminosis D. Hypovitaminosis D is common in countries at high latitudes, such as Ireland (53 N). The aim of this study was to measure serum vitamin D levels in consecutive patients (both asthmatic and non-asthmatic) with respiratory symptoms. Body mass index (BMI) was calculated following standard protocols. Blood samples were obtained and serum was tested for total immunoglobulin E (IgE), high sensitive C-reactive protein (hsCRP), 25-hydroxyvitamin D (25(OH)D) levels and eosinophil cationic protein (ECP). Serum total IgE and hsCRP were measured on the Abbott Architect ci8200 analyser. Total 25(OH)D was analyzed using the DiaSorin LIAISON. ECP was tested by ImmunoCAP Technology using fluorescent enzyme immunoassays on the IDM Phadia 250. Additionally, to evaluate the severity of airway disease; spirometry was performed to ascertain the Forced Expiratory Volume (FEV1) – a measure of lung function. All statistical analyses were performed using SigmaStat 3.0(SPSS) software. We examined 42 Caucasian adults (mean age 50.9 17.2; mean BMI 27.4 kg/m 5.9) with respiratory symptoms of more than 4 weeks (FEV1, 89 24% predicted. The average serum vitamin D level was 38.3 21.3 nmol/L. Vitamin D levels were positively associated with FEV1 (r = 0.33, p = 0.018). Moreover, all patients with airway obstruction (FEV1 less than 80% predicted) had vitamin D insufficiency (<80 nmol/L) and 50% were vitamin D deficient (<25 nmol/L). Markers of inflammation (ECP, hsCRP) and allergic immunity (IgE) were elevated in the vitamin D deficient state compared to sufficiency, but these differences were non-significant. All patients with IgE>500 IU/mL had deficient levels of 25(OH). We conclude that vitamin D deficiency is common in Irish patients with airway disease. Using the recently revised Institute of Medicine’s criterion for vitamin D deficiency of total 25(OH)D (<50 nmol/L), approximately 80% of the patients in the study had evidence of vitamin D deficiency. Vitamin D has emerged as an important immunomodulator with diverse benefits in respiratory disorders, for example antimicrobial peptide production. In addition, corticosteroid therapy is commonly prescribed for respiratory disorders, including asthma and chronic bronchitis, thus careful consideration should be made regarding bone health in patients with symptomatic airway obstruction. Our findings add to the growing evidence suggesting vitamin D may play an important role in airway disease.

/pdf/serum-vitamin-d-and-its-association-with-lung-function-and-461yk22tqc.pdf

Kenneth Bolger

Papers

Serum vitamin D and its association with lung function and inflammation in subjects with respiratory symptoms