Panoply™ Human TNFSF13B Knockdown Stable Cell Line

Senescent cells release a variety of cytokines, proteases, and growth factors, collectively known as the senescence-associated secretory phenotype (SASP). Persistent SASP contributes to chronic inflammation associated with aging and is closely linked to various age-related diseases. Here, researchers investigated the expression and function of BAFF (B-cell activating factor, encoded by the TNFSF13B gene)-an immunomodulatory cytokine and SASP component-across multiple models of senescence. The researchers first analyzed BAFF production in various senescence models, including senescent human diploid fibroblasts (WI-38, IMR-90), monocytic leukemia cells (THP-1), and mouse tissues undergoing induced senescence. Subsequently, they identified IRF1 (interferon regulatory factor 1) as the transcription factor required to drive TNFSF13B mRNA transcription during senescence. They found that inhibiting BAFF production attenuated the senescence phenotype in fibroblasts and monocyte-like cells, as evidenced by reduced IL-6 secretion and decreased SA-β-Gal staining. Notably, the impact of BAFF on senescence was cell-type specific: in monocytes, BAFF promoted early NF-κB activation and overall SASP secretion, whereas in fibroblasts, it was involved in the production and function of TP53 (p53). These results indicate that BAFF is highly expressed across various senescence models and represents a potential target for senotherapy.

In BAFF-knockdown THP-1 cells, the proportion of SA-β-Gal-positive cells decreased, a change that likely influenced other senescence characteristics (Figure 1A). Given that RNA-seq analysis suggested a role for BAFF in inflammation-and considering that senescent monocytes are characterized by increased secretion of pro-inflammatory molecules-the researchers investigated whether BAFF promotes the senescence-associated secretory phenotype (SASP) via an autocrine mechanism. RT-qPCR analysis revealed that ionizing radiation (IR) induced elevated mRNA levels of pro-inflammatory factors (such as IL8, IL1B, MMP9, and CCL2; Figure 1B), whereas BAFF knockdown reduced these levels. Assessments of cytokines, chemokines, and metalloproteinases using multiplex ELISA and cytokine arrays (Figure 1C) demonstrated a general reduction in SASP-related factors in BAFF-knockdown THP-1 cells.

Figure 1. BAFF silencing reduces senescence traits in irradiated monocytes. (Rossi M, et al., 2023)