ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization

Shi Zhang; Yao Liu; Xiao-Long Zhang; Yun Sun; Zhong-Hua Lu

doi:10.1016/j.jtauto.2023.100228

ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization

J Transl Autoimmun. 2023 Dec 21:8:100228. doi: 10.1016/j.jtauto.2023.100228. eCollection 2024 Jun.

Authors

Shi Zhang^{1

2}, Yao Liu³, Xiao-Long Zhang⁴, Yun Sun⁵, Zhong-Hua Lu⁵

Affiliations

¹ Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, ZhongdaHospital, Southeast University, Nanjing, Jiangsu, China.
² Department of Pulmonary and Critical Care Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
³ Emergency Department of Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Gulou District, Nanjing, China.
⁴ Department of Ultrasound, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁵ The First Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, China.

Abstract

Acute respiratory distress syndrome (ARDS) is independently associated with a poor prognosis in patients with sepsis. Macrophage M1 polarization plays an instrumental role in this process. Therefore, the exploration of key molecules affecting acute lung injury and macrophage M1 polarization may provide therapeutic targets for the treatment of septic ARDS. Here, we identified that elevated levels of Ankyrin repeat domain-containing protein 22 (ANKRD22) were associated with poor prognosis and more pronounced M1 macrophage polarization in septic patients by analyzing high-throughput data. ANKRD22 expression was also significantly upregulated in the alveolar lavage fluid, peripheral blood, and lung tissue of septic ARDS model mice. Knockdown of ANKRD22 significantly attenuated acute lung injury in mice with sepsis-induced ARDS and reduced the M1 polarization of lung macrophages. Furthermore, deletion of ANKRD22 in macrophages inhibited M1 macrophage polarization and reduced levels of phosphorylated IRF3 and intracellular interferon regulatory factor 3 (IRF3) expression, while re-expression of ANKRD22 reversed these changes. Further experiments revealed that ANKRD22 promotes IRF3 activation by binding to mitochondrial antiviral-signaling protein (MAVS). In conclusion, these findings suggest that ANKRD22 promotes the M1 polarization of lung macrophages and exacerbates sepsis-induced ARDS.

Keywords: ANKRD22; Acute lung injury; Acute respiratory distress syndrome (ARDS); Inflammatory response; Macrophage; Sepsis.