P75NTR activation limits CD21lo B cell subsets expansion in response to autoimmune-inducing challenges

Summary: Studies, including our own, suggest that p75NTR plays a pivotal role in immune regulation. Here, we aimed to uncover the role of p75NTR signaling in regulating CD21lo B cell subsets, which are known to facilitate autoimmune activity, and to identify possible regulatory transcripts involved....

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Main Authors: Cong Luo, An-Hui Zha, Ru-Yi Luo, Zhao-Lan Hu, Wei-Yun Shen, Ru-Ping Dai
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225013161
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Summary:Summary: Studies, including our own, suggest that p75NTR plays a pivotal role in immune regulation. Here, we aimed to uncover the role of p75NTR signaling in regulating CD21lo B cell subsets, which are known to facilitate autoimmune activity, and to identify possible regulatory transcripts involved. Through in vitro assays, in vivo models, and RNA-seq analysis, we found that p75NTR expression and CD21lo B cell expansion were increased in B cells following TLR7/9 stimulation in vitro and in pristane-challenged mice in vivo. Interestingly, p75NTR deficiency led to a further expansion of CD21lo B cells and enhanced their pro-inflammatory characteristics. RNA-seq data revealed notable transcript alterations associated with CD21lo B cells, including increased Tbx21 expression. A potential role for p75NTR downstream signaling via phosphorylated p65 (p-p65) was also proposed. Our study provides insights into the role of p75NTR in restraining the development of CD21lo subsets and modulating autoimmune activity in response to autoimmune challenges.
ISSN:2589-0042