tetano
Editor, Senior Moderator
Immunity
. 2023 Jul 4;S1074-7613(23)00271-6.
doi: 10.1016/j.immuni.2023.06.013. Online ahead of print. Expression of the readthrough transcript CiDRE in alveolar macrophages boosts SARS-CoV-2 susceptibility and promotes COVID-19 severity
Yuichi Mitsui[SUP] 1 [/SUP], Tatsuya Suzuki[SUP] 2 [/SUP], Kanako Kuniyoshi[SUP] 3 [/SUP], Jun Inamo[SUP] 4 [/SUP], Kensuke Yamaguchi[SUP] 4 [/SUP], Mariko Komuro[SUP] 3 [/SUP], Junya Watanabe[SUP] 3 [/SUP], Mio Edamoto[SUP] 3 [/SUP], Songling Li[SUP] 5 [/SUP], Tsukasa Kouno[SUP] 6 [/SUP], Seiya Oba[SUP] 7 [/SUP], Tadashi Hosoya[SUP] 7 [/SUP], Kentaro Masuhiro[SUP] 8 [/SUP], Yujiro Naito[SUP] 8 [/SUP], Shohei Koyama[SUP] 8 [/SUP], Nobuo Sakaguchi[SUP] 9 [/SUP], Daron M Standley[SUP] 5 [/SUP], Jay W Shin[SUP] 6 [/SUP], Shizuo Akira[SUP] 10 [/SUP], Shinsuke Yasuda[SUP] 7 [/SUP], Yasunari Miyazaki[SUP] 11 [/SUP], Yuta Kochi[SUP] 4 [/SUP], Atsushi Kumanogoh[SUP] 8 [/SUP], Toru Okamoto[SUP] 12 [/SUP], Takashi Satoh[SUP] 13 [/SUP]
Affiliations
Lung infection during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the angiotensin-I-converting enzyme 2 (ACE2) receptor induces a cytokine storm. However, the precise mechanisms involved in severe COVID-19 pneumonia are unknown. Here, we showed that interleukin-10 (IL-10) induced the expression of ACE2 in normal alveolar macrophages, causing them to become vectors for SARS-CoV-2. The inhibition of this system in hamster models attenuated SARS-CoV-2 pathogenicity. Genome-wide association and quantitative trait locus analyses identified a IFNAR2-IL10RB readthrough transcript, COVID-19 infectivity-enhancing dual receptor (CiDRE), which was highly expressed in patients harboring COVID-19 risk variants at the IFNAR2 locus. We showed that CiDRE exerted synergistic effects via the IL-10-ACE2 axis in alveolar macrophages and functioned as a decoy receptor for type I interferons. Collectively, our data show that high IL-10 and CiDRE expression are potential risk factors for severe COVID-19. Thus, IL-10R and CiDRE inhibitors might be useful COVID-19 therapies.
Keywords: M2c macrophage polarization; SARS-CoV-2; active readthrough transcript; hybrid receptor: CiDRE; innate immunity.
. 2023 Jul 4;S1074-7613(23)00271-6.
doi: 10.1016/j.immuni.2023.06.013. Online ahead of print. Expression of the readthrough transcript CiDRE in alveolar macrophages boosts SARS-CoV-2 susceptibility and promotes COVID-19 severity
Yuichi Mitsui[SUP] 1 [/SUP], Tatsuya Suzuki[SUP] 2 [/SUP], Kanako Kuniyoshi[SUP] 3 [/SUP], Jun Inamo[SUP] 4 [/SUP], Kensuke Yamaguchi[SUP] 4 [/SUP], Mariko Komuro[SUP] 3 [/SUP], Junya Watanabe[SUP] 3 [/SUP], Mio Edamoto[SUP] 3 [/SUP], Songling Li[SUP] 5 [/SUP], Tsukasa Kouno[SUP] 6 [/SUP], Seiya Oba[SUP] 7 [/SUP], Tadashi Hosoya[SUP] 7 [/SUP], Kentaro Masuhiro[SUP] 8 [/SUP], Yujiro Naito[SUP] 8 [/SUP], Shohei Koyama[SUP] 8 [/SUP], Nobuo Sakaguchi[SUP] 9 [/SUP], Daron M Standley[SUP] 5 [/SUP], Jay W Shin[SUP] 6 [/SUP], Shizuo Akira[SUP] 10 [/SUP], Shinsuke Yasuda[SUP] 7 [/SUP], Yasunari Miyazaki[SUP] 11 [/SUP], Yuta Kochi[SUP] 4 [/SUP], Atsushi Kumanogoh[SUP] 8 [/SUP], Toru Okamoto[SUP] 12 [/SUP], Takashi Satoh[SUP] 13 [/SUP]
Affiliations
- PMID: 37442134
- DOI: 10.1016/j.immuni.2023.06.013
Lung infection during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the angiotensin-I-converting enzyme 2 (ACE2) receptor induces a cytokine storm. However, the precise mechanisms involved in severe COVID-19 pneumonia are unknown. Here, we showed that interleukin-10 (IL-10) induced the expression of ACE2 in normal alveolar macrophages, causing them to become vectors for SARS-CoV-2. The inhibition of this system in hamster models attenuated SARS-CoV-2 pathogenicity. Genome-wide association and quantitative trait locus analyses identified a IFNAR2-IL10RB readthrough transcript, COVID-19 infectivity-enhancing dual receptor (CiDRE), which was highly expressed in patients harboring COVID-19 risk variants at the IFNAR2 locus. We showed that CiDRE exerted synergistic effects via the IL-10-ACE2 axis in alveolar macrophages and functioned as a decoy receptor for type I interferons. Collectively, our data show that high IL-10 and CiDRE expression are potential risk factors for severe COVID-19. Thus, IL-10R and CiDRE inhibitors might be useful COVID-19 therapies.
Keywords: M2c macrophage polarization; SARS-CoV-2; active readthrough transcript; hybrid receptor: CiDRE; innate immunity.