Regulatory T cells and type 2 innate lymphoid cell‐dependent asthma

Group 2 innate lymphoid cells (ILC2s) are a recently identified group of cells with the potent capability to produce Th2‐type cytokines such as interleukin (IL)‐5 and IL‐13. Several studies suggest that ILC2s play an important role in the development of allergic diseases and asthma. Activation of pulmonary ILC2s in murine models lacking T and B cells induces eosinophilia and airway hyper‐reactivity (AHR), which are cardinal features of asthma. More importantly, numerous recent studies have highlighted the role of ILC2s in asthma persistence and exacerbation among human subjects, and thus, regulation of pulmonary ILC2s is a major area of investigation aimed at curbing allergic lung inflammation and exacerbation. Emerging evidence reveals that a group of regulatory T cells, induced Tregs (iTregs), effectively suppress the production of ILC2‐driven, pro‐inflammatory cytokines IL‐5 and IL‐13. The inhibitory effects of iTregs are blocked by preventing direct cellular contact or by inhibiting the ICOS‐ICOS‐ligand (ICOSL) pathway, suggesting that both direct contact and ICOS‐ICOSL interaction are important in the regulation of ILC2 function. Also, cytokines such as IL‐10 and TGF‐β1 significantly reduce cytokine secretion by ILC2s. Altogether, these new findings uncover iTregs as potent regulators of ILC2 activation and implicate their utility as a therapeutic approach for the treatment of ILC2‐mediated allergic asthma and respiratory disease.     

2型固有淋巴样细胞与哮喘

一直以来,2型辅助T淋巴细胞（Th2）被认为是通过分泌2型细胞因子介导哮喘患者气道慢性炎症反应的主要维持者.但其仍无法解释许多哮喘相关现象.近年来人们发现的2型固有淋巴样细胞（ILC2s）可以不依赖于固有免疫系统,在IL-25、IL-33或胸腺基质淋巴生成素（TSLP）等的作用下对外界多种刺激产生反应,分泌2型细胞因子,引发并维持2型免疫炎症反应,与人体抗寄生虫免疫、过敏相关疾病息息相关.     

Polymorphonuclear myeloid-derived suppressor cells attenuate allergic airway inflammation by negatively regulating group 2 innate lymphoid cells

Hyperactivation of the type 2 immune response is the major mechanism of allergic asthma, in which both group 2 innate lymphoid cells (ILC2s) and type 2 helper T (Th2) cells participate. Myeloid-derived suppressor cells (MDSCs) alleviate asthma by suppressing Th2 cells. However, the potential effects of MDSCs on the biological functions of ILC2s remain largely unknown. Here, we examined the roles of MDSCs (MDSCs) in the modulation of ILC2 function. Our results showed that polymorphonuclear (PMN)-MDSCs, but not monocytic (M-) MDSCs, effectively suppressed the cytokine production of ILC2s both in vitro and in vivo, thereby alleviating airway inflammation. Further analyses showed that cyclo-oxygenase-1 may mediate the suppressive effects of PMN-MDSCs on ILC2 responses. Our findings demonstrated that PMN-MDSCs may serve as a potent therapeutic target for the treatment of ILC2-driven allergic asthma.     

Interplay of innate lymphoid cells and the microbiota

Innate lymphoid cells (ILC) are a recently identified group of innate lymphocytes that are preferentially located at barrier surfaces. Barrier surfaces are in direct contact with complex microbial ecosystems, collectively referred to as the microbiota. It is now believed that the interplay of the microbiota with host components (i.e. epithelial cells and immune cells) promotes host fitness by regulating organ homeostasis, metabolism, and host defense against pathogens. In this review, we will give an overview of this multifaceted interplay between ILC and components of the microbiota.     

Group 2 innate lymphoid cells in lung inflammation

Although allergic asthma is a heterogeneous disease, allergen‐specific T helper 2 (Th2) cells producing the key cytokines involved in type 2 inflammation, interleukin‐4 (IL‐4), IL‐5 and IL‐13, are thought to play a major role in asthma pathogenesis. This model is challenged by the recent discovery of group 2 innate lymphoid cells (ILC2) that represent a critical innate source of type 2 cytokines. These ILC2 are activated by epithelial cell‐derived cytokines, including IL‐25 and IL‐33, which have been implicated in the initiation of asthma. In this review, we will discuss recent studies supporting a significant role for ILC2 in lung inflammation, with special attention to allergen‐induced asthma.     

Extracellular DNA traps in bronchoalveolar fluid from a murine eosinophilic pulmonary response

Asthma is associated with a loss of the structural integrity of airway epithelium and dysfunction of the physical barrier, which protects airways from external harmful factors. Granulocyte activation causes the formation of extracellular traps, releasing web‐like structures of DNA and proteins, being important to kill pathogens extracellularly. We investigated whether eosinophils infiltrating airways in an experimental model of asthma would induce eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid and lung tissue. We showed that an ovalbumin (OVA) asthma protocol presented a significant increase in eosinophil counts with increased extracellular DNA in bronchoalveolar lavage fluid as well as in lung tissue, confirming the presence of DNA traps colocalized with eosinophil peroxidase. EETs formation was reversed by DNase treatment. With these approaches, we demonstrated for the first time that OVA‐challenged mice release extracellular DNA traps, which could aggravate pulmonary dysfunction.     

Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response

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