iNKT cells with high PLZF expression are recruited into the lung via CCL21‐CCR7 signaling to facilitate the development of asthma tolerance in mice,European Journal of Immunology

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iNKT cells with high PLZF expression are recruited into the lung via CCL21‐CCR7 signaling to facilitate the development of asthma tolerance in mice
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-07-26 , DOI: 10.1002/eji.202048798
Xintong Feng _{1,

2} , Caiqi Zhao ₃ , Ling Li ₃ , Jingjing Feng _{1,

2} , Wei He _{1,

2} , Tianyun Shi _{1,

2} , Na Li _{1,

2} , Zhijun Jie _{1,

2} , Xiao Su ₃

Affiliation

Establishment of immune tolerance is crucial to protect humans against asthma. Promyelocytic leukemia zinc finger (PLZF) is an emerging suppressor of inflammatory responses. CCL21‐CCR7 signaling mediates tolerance development. However, whether PLZF and CCL21‐CCR7 are required for the development of asthma tolerance is unknown. Here, we found that Zbtb16 (coding PLZF) and Ccl21 were upregulated in OVA‐induced asthma tolerance (OT) lungs by RNA‐seq. PLZF physically interacted with GATA3 and its expression was higher in GATA3⁺ Th2 cells and ILC2s in OT lungs. Zbtb16‐knockdown in lymphocytes promoted the differentiation of CD3e⁺CD4⁺ T cells, particularly those producing IL‐4 and IL‐5. Moreover, iNKT cells with high expression of PLZF were recruited into the lungs via draining lymph nodes during tolerance. Blockade of CCL21‐CCR7 signaling in OT mice decreased the PLZF⁺ cell population, abolished CCR7‐induced PLZF⁺ iNKT recruitment to the lungs, enhanced Th2responses and exacerbated lung pathology. In OT mice, respiratory syncytial virus (RSV) infection impeded PLZF⁺ cell and CCR7⁺PLZF⁺ iNKT cellrecruitment to the lungs and increased airway resistance. Collectively, these results indicate that PLZF could interact with GATA3 and restrain differentiation of IL‐4‐ and IL‐5‐producing T cells, iNKT cells with high PLZF expression are recruited to the lungs via CCL21‐CCR7 signaling to facilitate the development of asthma tolerance.

中文翻译：

高PLZF表达的iNKT细胞通过CCL21-CCR7信号募集入肺，以促进小鼠哮喘耐受性的发展

免疫耐受的建立对于保护人类免受哮喘至关重要。早幼粒细胞白血病锌指（PLZF）是一种新兴的炎症反应抑制剂。CCL21-CCR7信号介导耐受性的发展。但是，未知是否需要PLZF和CCL21-CCR7来发展哮喘耐受性。在这里，我们发现RNA序列在OVA诱导的哮喘耐受（OT）肺中上调了Zbtb16（编码PLZF）和Ccl21。PLZF与GATA3物理相互作用，在OT肺的GATA3 ⁺ Th2细胞和ILC2s中表达较高。淋巴细胞的Zbtb16基因敲低促进CD3e ⁺ CD4 ⁺的分化T细胞，特别是产生IL-4和IL-5的T细胞。此外，在耐受期间，通过排泄淋巴结将具有高表达PLZF的iNKT细胞募集入肺。OT小鼠中CCL21-CCR7信号的阻断减少了PLZF ⁺细胞数量，废除了CCR7诱导的PLZF ⁺ iNKT向肺的募集，增强了Th2反应并加剧了肺部病理。在OT小鼠中，呼吸道合胞病毒（RSV）感染阻碍了PLZF ⁺ 细胞和CCR7 ⁺ PLZF ⁺iNKT细胞招募至肺部并增加气道阻力。总的来说，这些结果表明PLZF可以与GATA3相互作用并抑制IL-4和IL-5产生的T细胞分化，具有高PLZF表达的iNKT细胞通过CCL21-CCR7信号募集到肺部，以促进哮喘的发展公差。

更新日期：2020-07-26

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