Alabed Mashael, Sultana Shaik Asma, Saheb Sharif-Askari Narjes, Saheb Sharif-Askari Fatemeh, Hafezi Shirin, Mdkhana Bushra, Ratemi Elaref, Al-Muhsen Saleh, Hamid Qutayba, Halwani Rabih
Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Department of Pediatrics, Immunology Research Lab, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Int Arch Allergy Immunol. 2022;183(2):127-141. doi: 10.1159/000518835. Epub 2021 Oct 20.
Memory T cells play a central role in regulating inflammatory responses during asthma. However, tissue distribution of effector memory (TEM) and central memory (TCM) T-cell subtypes, their differentiation, and their contribution to the persistence of lung tissue inflammation during asthma are not well understood. Interestingly, an increase in survival and persistence of memory T cells was reported in asthmatic lungs, which may suggest a shift toward the more persistent TCM phenotype. In this report, we investigated the differential distribution of memory T-cell subtypes during allergic lung inflammation and the mechanism regulating that. Using an OVA-sensitized asthma mouse model, we observed a significant increase in the frequency of TCM cells in inflamed lungs compared to healthy controls. Interestingly, adoptive transfer techniques confirmed substantial infiltration of TCM cells to lung tissues during allergic airway inflammation. Expression levels of TCM homing receptors, CD34 and GlyCAM-1, were also significantly upregulated in the lung tissues of OVA-sensitized mice, which may facilitate the increased TCM infiltration into inflamed lungs. Moreover, a substantial increase in the relative expression of TCM profile-associated genes (EOMES, BCL-6, ID3, TCF-7, BCL-2, BIM, and BMI-1) was noted for TEM cells during lung inflammation, suggesting a shift for TEM into the TCM state. To our knowledge, this is the first study to report an increased infiltration of TCM cells into inflamed lung tissues and to suggest differentiation of TEM to TCM cells in these tissues. Therapeutic interference at TCM infiltration or differentiations could constitute an alternative treatment approach for lung inflammation.
记忆T细胞在哮喘期间调节炎症反应中起核心作用。然而，效应记忆（TEM）和中枢记忆（TCM）T细胞亚群的组织分布、它们的分化以及它们在哮喘期间对肺组织炎症持续存在的贡献尚未得到充分了解。有趣的是，有报道称哮喘肺中记忆T细胞的存活和持久性增加，这可能表明向更持久的TCM表型转变。在本报告中，我们研究了过敏性肺炎症期间记忆T细胞亚群的差异分布及其调节机制。使用卵清蛋白致敏的哮喘小鼠模型，我们观察到与健康对照相比，炎症肺中TCM细胞的频率显著增加。有趣的是，过继转移技术证实了在过敏性气道炎症期间TCM细胞大量浸润到肺组织中。OVA致敏小鼠肺组织中TCM归巢受体CD34和GlyCAM-1的表达水平也显著上调，这可能促进TCM向炎症肺的浸润增加。此外，在肺部炎症期间，TEM细胞中与TCM特征相关基因（EOMES、BCL-6、ID3、TCF-7、BCL-2、BIM和BMI-1）的相对表达大幅增加，表明TEM向TCM状态转变。据我们所知，这是第一项报道TCM细胞向炎症肺组织浸润增加并提示这些组织中TEM向TCM细胞分化的研究。对TCM浸润或分化进行治疗干预可能构成一种治疗肺部炎症的替代方法。
