COVID-19肺炎重症患者におけるIL-2/IL-2Rの阻害は、JAK1-STAT5を介してCD8 T細胞とリンパ球の減少をもたらす

The inhibition of IL-2/IL-2R gives rise to CD8 T cell and lymphocyte decrease through JAK1-STAT5 in critical patients with COVID-19 pneumonia.

• Hongbo Shi
• Wenjing Wang
• Jiming Yin
• Yabo Ouyang
• Lijun Pang
• Yingmei Feng
• Luxin Qiao
• Xianghua Guo
• Honglin Shi
• Ronghua Jin
• Dexi Chen

抄録

COVID-19肺炎のほとんどの患者は予後良好であるが、一部の患者は重症化・重症化し、重症化した場合の死亡率は61.5％に上る。しかし，COVID-19 肺炎重症患者における免疫応答に関する特異的な分子情報は十分に理解されていない．合計54人の患者が登録され、3つのグループに分けられたが、そのうち一般的なものが34人、重症が14人、重症が6人であった。患者の末梢血単核球（PBMC）の体質をCyTOFで解析した。ルミネックスを用いて患者の血漿中のサイトカインのプロファイルを調べた。患者のPBMCにおけるIL-2シグナル伝達経路をqRT-PCRで調べた。重症患者では、COVID-19肺炎の一般的な重症患者と比較して、リンパ球の数と割合が有意に減少した。重症患者では，T細胞，B細胞，NK細胞の数が健常者と比較して有意に減少した．CD8 T細胞の割合は，重症患者ではCOVID-19肺炎の一般患者および重症患者に比べて有意に低かった．IL-2R、JAK1、STAT5の発現は、一般患者、重症患者、重症患者、重症患者のPBMCで減少したが、IL-2レベルは重症患者で上昇し、COVID-19肺炎の重症患者では減少した。COVID-19肺炎の重症患者におけるCD8 T細胞の減少は、IL-2シグナル伝達経路と関連している可能性がある。IL-2/IL-2R の阻害は、COVID-19 肺炎の重症患者における JAK1-STAT5 を介した CD8 T 細胞およびリンパ球の減少をもたらします。

Although most patients with COVID-19 pneumonia have a good prognosis, some patients develop to severe or critical illness, and the mortality of critical cases is up to 61.5%. However, specific molecular information about immune response in critical patients with COVID-19 is poorly understood. A total of 54 patients were enrolled and divided into three groups, among which 34 were common, 14 were severe, and 6 were critical. The constitution of peripheral blood mononuclear cells (PBMC) in patients was analyzed by CyTOF. The profile of cytokines was examined in plasma of patients using luminex. The IL-2 signaling pathway was investigated in the PBMC of patients by qRT-PCR. The count and percentage of lymphocytes were significantly decreased in critical patients compared to common and severe patients with COVID-19 pneumonia. The count of T cells, B cells, and NK cells was remarkably decreased in critical patients compared to normal controls. The percentage of CD8 T cells was significantly lower in critical patients than that in common and severe patients with COVID-19 pneumonia. The expression of IL-2R, JAK1, and STAT5 decreased in PBMC of common, severe, and critical patients, but IL-2 level was elevated in severe patients and decreased in critical patients with COVID-19 pneumonia. The decrease of CD8 T cells in critical patients with COVID-19 pneumonia may be related to the IL-2 signaling pathway. The inhibition of IL-2/IL-2R gives rise to CD8 T cell and lymphocyte decrease through JAK1-STAT5 in critical patients with COVID-19 pneumonia.