Regulatory cytokine function in the respiratory tract

Abstract

The respiratory tract is an important site of immune regulation; required to allow protective immunity against pathogens, while minimizing tissue damage and avoiding aberrant inflammatory responses to inhaled allergens. Several cell types work in concert to control pulmonary immune responses and maintain tolerance in the respiratory tract, including regulatory and effector T cells, airway and interstitial macrophages, dendritic cells and the airway epithelium. The cytokines transforming growth factor β, interleukin (IL-) 10, IL-27, and IL-35 are key coordinators of immune regulation in tissues such as the lung. Here, we discuss the role of these cytokines during respiratory infection and allergic airway disease, highlighting the critical importance of cellular source and immunological context for the effects of these cytokines in vivo.

A T cell–myeloid IL-10 axis regulates pathogenic IFN-γ–dependent immunity in a mouse model of type 2–low asthma

“…Pulmonary immunity must be tightly regulated by anti-inflammatory cytokines to minimize tissue damage that might compromise respiratory function. 18 Asthma is thought to occur because of an imbalance between immune activation and regulation in the respiratory tract, prompting efforts to boost regulatory mechanisms by immunotherapy to treat allergic diseases. 54 The cytokine IL-10 can regulate diverse T H cell responses to limit immunopathology, 11 including T2 immunity in murine models of asthma.…”

“…11,16,17 Therefore IL-10 can act through diverse mechanisms to limit pulmonary immunopathology in different contexts. 18 T H cell-derived IL-10 is a key mediator of induced tolerance to allergens 19,20 and resolution of allergic inflammation. 21 Conversely, impaired IL-10 production by T H cells has been reported in patients with severe asthma, 22,23 and genetic variants affecting IL-10 expression have been associated with asthma incidence and severity.…”

“…24,25 However, despite these associations, the mechanisms by which IL-10 regulates diverse immunologic phenotypes of asthma are incompletely understood. 18 Mechanistic studies in asthma frequently use murine models of allergic airway disease (AAD) typically involving peripheral sensitization to a model allergen followed by airway allergen challenge. 26 These protocols bypass the APC network of the lungs, which is essential for sensitization to inhaled allergens, 27 and generate a highly polarized T2 response that does not reflect the heterogeneous immunologic phenotypes observed in human asthma.…”

The Relationship of IL-8 and IL-10 Myokines and Performance in Male Marathon Runners Presenting Exercise-Induced Bronchoconstriction

“…In relation to marathons, our group previously demonstrated that marathon runners who had increased IL-10 levels in the circulation immediately after the marathon and also in the nasal mucosa 72 hours after the marathon did not present upper respiratory symptoms [12,33]. In addition, it has been also reported that systemic IL-10 can modulate the pulmonary function by modulating the inflammatory response of the airways [29,45], including that associated with physical exercise [50,51]. However, studies that aimed to evaluate the effect of IL-10 in the context of EIB are scarce [52,53].…”

“…Cytokines are proteins that present many functions, such as the regulation of inflammatory responses, chemotaxis, and cell activation, among others [28,29]. During physical exercise, muscle contractions elicit the release of several molecules, including cytokines such as IL-1ra, IL-6, IL-8, IL-10, and TNF-α [30,31].…”