Israr Mohd, Lam Fung, DeVoti James, Mace Emily M, Papayannakos Christopher, Abramson Allan, Steinberg Bettie M, Bonagura Vincent R
The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia Medical Center, NY, USA.
Eur J Immunol. 2023 Apr;53(4):e2250036. doi: 10.1002/eji.202250036. Epub 2023 Jan 31.
Recurrent respiratory papillomatosis (RRP), a rare chronic disease caused primarily by human papillomavirus types 6 and 11, consists of repeated growth of premalignant papillomas in the airway. RRP is characterized by multiple abnormalities in innate and adaptive immunity. Natural killer (NK) cells play important roles in immune surveillance and are part of the innate immune responses that help prevent tumor growth. We identified that papillomas lack classical class I MHC and retain nonclassical class I MHC expression. Moreover, in this study, we have identified and characterized the mechanism that blocks NK cell targeting of papilloma cells. Here, we show for the first time that the PGE secreted by papilloma cells directly inhibits NK cells activation/degranulation principally through the PGE receptor EP2, and to a lesser extent through EP4 signaling. Thus, papilloma cells have a potent mechanism to block NK cell function that likely supports papilloma cell growth.
复发性呼吸道乳头状瘤病（RRP）是一种主要由6型和11型人乳头瘤病毒引起的罕见慢性疾病，其特征是气道中癌前乳头状瘤反复生长。RRP的特点是先天性和适应性免疫存在多种异常。自然杀伤（NK）细胞在免疫监视中起重要作用，是有助于预防肿瘤生长的先天性免疫反应的一部分。我们发现乳头状瘤缺乏经典的I类主要组织相容性复合体（MHC），并保留非经典I类MHC表达。此外，在本研究中，我们已经确定并描述了阻止NK细胞靶向乳头状瘤细胞的机制。在这里，我们首次表明，乳头状瘤细胞分泌的前列腺素E（PGE）主要通过PGE受体EP2直接抑制NK细胞的激活/脱颗粒，在较小程度上通过EP4信号传导。因此，乳头状瘤细胞有一种有效的机制来阻断NK细胞功能，这可能支持乳头状瘤细胞的生长。
