Stat6 is known to drive macrophage M2 polarization. However, how macrophage polarization is fine-tuned by Stat6 is poorly understood. Here, we find that Lys383 of Stat6 is acetylated by the acetyltransferase CREB-binding protein (CBP) during macrophage activation to suppress macrophage M2 polarization. Mechanistically, Trim24, a CBP-associated E3 ligase, promotes Stat6 acetylation by catalyzing CBP ubiquitination at Lys119 to facilitate the recruitment of CBP to Stat6. Loss of Trim24 inhibits Stat6 acetylation and thus promotes M2 polarization in both mouse and human macrophages, potentially compromising antitumor immune responses. By contrast, Stat6 mediates the suppression of TRIM24 expression in M2 macrophages to contribute to the induction of an immunosuppressive tumor niche. Taken together, our findings establish Stat6 acetylation as an essential negative regulatory mechanism that curtails macrophage M2 polarization.

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Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of autoantibodies by plasma cells. Although the functional importance of plasma cells and autoantibodies in SLE has been well established, the underlying molecular mechanisms of controlling autoantibody production remain poorly understood. Here we show that Peli1 has a B cell-intrinsic function to protect against lupus-like autoimmunity in mice. Peli1 deficiency in B cells induces autoantibody production via noncanonical NF-κB signaling. Mechanically, Peli1 functions as an E3 ligase to associate with NF-κB inducing kinase (NIK) and mediates NIK Lys48 ubiquitination and degradation. Overexpression of Peli1 inhibits noncanonical NF-κB activation and alleviates lupus-like disease. In humans, PELI1 levels negatively correlate with disease severity in SLE patients. Our findings establish Peli1 as a negative regulator of the noncanonical NF-κB pathway in the context of restraining the pathogenesis of lupus-like disease.

The alpine wetlands on the Tibetan Plateau (TP) constitute 30% of China's wetlands, and previous studies have considered these wetlands to be important sources of CH 4 , based on several swamp measurements from the eastern edges of the plateau. However, the alpine wetlands consist of both swamps (9.5%) and swamp meadows (79.8%). In this study, the CH 4 fluxes of a swamp meadow and a swamp were determined. The results showed that the swamp meadow emitted much less CH 4 (130.8 ± 123.9 μg). The CH 4 fluxes within the swamp meadow showed distinct microscale spatial heterogeneity: the hollow terrain released CH 4 , while the hummocks absorbed CH 4 ; this pattern was explained well by soil moisture. The CH 4 emissions in the swamp meadow were highly sensitive to soil temperature variation (Q 10 = 3.62), while they were more sensitive to soil moisture in the swamp. By summarizing existing measurements, and considering the differences in CH 4 emissions from swamp meadows and swamps, the emissions of CH 4 from alpine wetlands across the TP were recalculated to range from 0.215 to 0.412 Tg CH 4 a À1 , lower than previous studies. By comparison, the CH 4 uptake by nonwetland ecosystems ranges from À0.68 to À0.53 Tg CH 4 a À1. Therefore, this study conveys a notion that the alpine wetlands on the TP may not be significant CH 4 sources. However, further studies are needed to reduce the uncertainty regarding CH 4 emissions.