Breaking Steroid Resistance: Effect of Vitamin D on IL-23.
Breaking Steroid Resistance: Effect of Vitamin D on IL-23.
复制标题
打破类固醇抵抗：维生素 D 对 IL-23 的影响。
DOI：
10.1165/rcmb.2017-0199ed
复制
发表时间：
2017
影响因子：
6.4
通讯作者：
Haczku,Angela
中科院分区：
文献类型：
--
作者：
Flayer,CameronH;Larson,ErikD;Haczku,Angela
Chronic exposure to air pollution can lead to altered respiratory mucosal immune function and predisposition to or exacerbation of chronic obstructive pulmonary disease (COPD) or asthma. These diseases are characterized by genetic bias, airway inflammation and remodeling, and activation of innate and adaptive respiratory immune pathways. Glucocorticoids are typically used to treat inflammation and immune cell activation in asthma and COPD, but severe cases may be resistant to treatment. T helper 17 (Th17) cells and IL-17–related pathways have been linked to both air pollution–induced airway inflammation and glucocorticoid resistance. In this issue of the Journal, Mann and colleagues (pp. 355–366) describe the effects of the air pollutant known as urban particulate matter (UPM) and vitamin D on dendritic cell (DC)-induced stimulation of Th17. 1 cells (1). They used an elegant myeloid DC-memory CD4 1 T cell coculture system to investigate the in vitro mechanisms of UPM-driven IL-17A and IL-22 production, and to address whether glucocorticoid-resistant Th17. 1 activation can be inhibited by vitamin D treatment (Figure 1). Exposure to UPM has been known to induce airway inflammation and impair lung function, and is implicated in the pathogenesis of asthma and COPD (2). In mouse models, functional changes in the airways after UPM inhalation were elicited by lymphocyte-derived cytokines (3). Indeed, T lymphocytes stimulated ex vivo with various types of UPM can produce IFN-g, IL-13, IL-17A, and IL-22, suggesting that UPM can induce activation of Th1, Th2, Th17, and Th22 cells, respectively (4, 5). However, UPM was also shown to suppress Th1 responses, indicating that the composition of UPM can drive various types of T cell responses (6). Recent evidence also suggests that the classical T cell subtype paradigm is less rigid than once thought. In fact, T cells can be programmed to produce cytokines characteristic of more than one subset based on extrinsic and intrinsic signals (7, 8). In the present study, Mann and colleagues set out to clarify precisely how UPM alters the cytokine output of T cells, because of the potential of this material to induce a variety of T cell responses (1). The authors found that UPM-primed DCs increased the proportion of memory CD4 1 T cells with a “Th17. 1-like”(9) proinflammatory phenotype. The importance of Th17. 1 cells originally emerged in the context of autoimmune diseases. It was shown that in the presence of IL-23 and IL-12, Th17 cells decreased IL-17A and (like Th1 cells) increased IFN-g production. Pathogenicity of these cells required IL-23 receptor activation and was abolished by blockade of IFN-g, but not of IL-17A (10). Indeed, Th17 cells display a remarkable developmental plasticity; share functional characteristics with inducible regulatory T, Th1, and Th22 cells; and coexpress the corresponding lineage-specific transcription factor (s) or cytokine (s)(11). Because this plasticity determines whether Th17 cells will serve immune-protective or pathogenic functions, it poses a major concern. As patients suffering from COPD or asthma are increasingly being grouped into distinct subphenotypes and endotypes based on the mechanisms that drive their disease (12–15), the ability to clarify how Th17 cells function is becoming particularly critical.In the current study, UPM-primed DCs induced CD4 T cells to produce the Th17-associated cytokines IL-17A, IL-17F, and IL-22, as well as IFN-g, granulocyte-macrophage colony-stimulating factor, and granzyme B. A large proportion of the UPM-driven IL-17A 1 cells coexpressed these cytokines, but not IL-10 or IL-13 (1). Notably, although IL-17A is a well …
