Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps.

Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps.
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第2组先天淋巴样细胞升高并在鼻息息肉中激活。

DOI:
10.1002/iid3.161
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发表时间:
2017-09
期刊:
Immunity, inflammation and disease
影响因子:
--
通讯作者:
Kato A
Kato A
中科院分区:
其他
文献类型:
--
作者:
Poposki JA;Klingler AI;Tan BK;Soroosh P;Banie H;Lewis G;Hulse KE;Stevens WW;Peters AT;Grammer LC;Schleimer RP;Welch KC;Smith SS;Conley DB;Raviv JR;Karras JG;Akbari O;Kern RC;Kato A

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慢性鼻窦炎(CRS)合并鼻息肉(CRSwNP)的特征是2型炎症伴高水平Th2细胞因子。虽然T辅助细胞因子是由T细胞释放的,但已知先天淋巴样细胞(ILC)也能产生高水平的T辅助细胞因子。然而,各种类型的ILC在CRS中的存在尚不清楚。本研究的目的是充分表征CRS中所有ILC亚群的存在,并确定CRSwNP中2组ILC (ILC2)与非2型炎症区域ILC2的表型差异。我们通过流式细胞术研究了健康人外周血单个核细胞(PBMC)、对照组和非息肉样CRS (CRSsNP)和CRSwNP患者的扁桃体组织、筛样组织以及来自CRSwNP的鼻息肉(NP)组织中ILC亚群的存在。分选后的ILC2在IL - 33存在和不存在的情况下培养,用Luminex评估IL - 5和IL - 13的产生。我们发现所有ILC亚群都存在于NP中,但ILC2占主导地位,与PBMC、扁桃体、CRSsNP和正常鼻窦组织相比,ILC2显著升高。我们还发现,与血液或扁桃体ILC2相比,NP组ILC2中的诱导型T细胞共刺激因子(ICOS)和侧散射增加,CD127下调。胸腺基质淋巴生成素、IL‐7和IL‐33能够下调CD127的表达并增加血液中ILC2的侧散度。此外,分类NP ILC2自发释放2型细胞因子,包括IL‐5和IL‐13,而血液ILC2不自发释放。这些结果提示,体内CRSwNP中ILC2不仅升高,而且被激活,ILC2可能在CRSwNP的2型炎症中发挥重要作用。
Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by type 2 inflammation with high levels of Th2 cytokines. Although T helper cytokines are released from T cells, innate lymphoid cells (ILC) are also known to produce high levels of the same cytokines. However, the presence of various types of ILC in CRS is poorly understood. The objective of this study was to fully characterize the presence of all ILC subsets in CRS and to identify phenotypical differences of group 2 ILC (ILC2) in CRSwNP compared to ILC2 from non‐type 2 inflamed areas. We investigated the presence of ILC subsets in peripheral blood mononuclear cells (PBMC) from healthy subjects, tonsil tissue, ethmoid tissue from control subjects and patients with non‐polypoid CRS (CRSsNP) and CRSwNP, as well as nasal polyp (NP) tissue from CRSwNP by flow cytometry. Sorted ILC2 were cultured in the presence and absence of IL‐33 and production of IL‐5 and IL‐13 was assessed by Luminex. We found that all ILC subsets were present in NP but ILC2 were dominant and significantly elevated compared to PBMC, tonsil, CRSsNP, and normal sinus tissue. We also found that inducible T‐cell co‐stimulator (ICOS) and side scatter were increased and CD127 was down‐regulated in ILC2 from NP compared to blood or tonsil ILC2. Thymic stromal lymphopoietin, IL‐7, and IL‐33 were able to down‐regulate expression of CD127 and increase side scatter in blood ILC2. Furthermore, sorted NP ILC2 but not blood ILC2 spontaneously released type 2 cytokines including IL‐5 and IL‐13. These results suggest that ILC2 are not only elevated but also activated in CRSwNP in vivo and that ILC2 may play important roles in the type 2 inflammation in CRSwNP.
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