To investigate the regulatory effect of TGF-β activated kinase-1-binding protein 1 (TAB1) on immunoparalysisrelated phenotypes and to provide a potential biomarker for prognosis assessment in severe pneumonia.

Based on the GSE65682 dataset, 183 patients with severe pneumonia and 42 healthy controls were enrolled, and the differential expression of TAB1 was analyzed. Univariate Cox proportional hazards regression model was used to evaluate the association between TAB1 expression and patient prognosis. Human monocytederived macrophages (MDMs) were used as a model, and TAB1 was knocked down by RNA interference. Flow cytometry, Western blot, and realtime quantitative polymerase chain reaction (PCR) were employed to detect phagocytic capacity, human leukocyte antigen DR (HLADR) expression, macrophage polarization, and changes in the transcriptional levels of proinflammatory cytokine genes.

(1) The expression level of TAB1 in peripheral blood was significantly higher in healthy controls than in patients with severe pneumonia (P<0.05), and significantly higher in survivors than in nonsurvivors (P<0.01). Univariate Cox regression analysis showed that high TAB1 expression was significantly associated with favorable prognosis (HR=0.029, 95%CI: 0.004~0.214, P<0.001). (2) Compared with the control group, the siTAB1 group exhibited a decreased phagocytosis rate (56.2% vs. 16.8%, P<0.001), an increased proportion of M2 macrophages (CD80^- CD206⁺ ) (7.33% vs. 32.4%, P<0.05), and significantly reduced HLADR protein expression (P<0.001). The mRNA relative expression levels of proinflammatory cytokines interleukin1β (IL1β), IL6, and tumor necrosis factor (TNF) were significantly downregulated (P<0.01).

High TAB1 expression is associated with favorable prognosis in severe pneumonia. Knockdown of TAB1 induces typical immunoparalysis phenotypes in MDMs, including phagocytic dysfunction, low HLADR expression, M2 polarization, and suppression of proinflammatory cytokines. TAB1 holds promise as a potential molecular biomarker for prognosis and immune status monitoring in severe pneumonia.