Why the study?
T follicular helper cells play a central role in humoral autoimmunity such as primary Sjögren’s syndrome, but targeting them remains challenging in clinical management.
The Cav-1/PPARα axis plays an unrecognized role in Tfh cell tolerance, suggesting PPARα activation with fenofibrate as a promising therapeutic target for humoral autoimmunity in Sjogren's syndrome.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for fenofibrate in Sjögren's syndrome; leaves open clinical translation from murine models.
T follicular helper (Tfh) cells play a central role in humoral autoimmunity, including primary Sjögren’s syndrome (pSS). However, targeting Tfh cells is challenging in clinical management. Previous studies suggested inducible Tcell costimulator (ICOS) directed Tfh cell motility in engaging bystander B cells. Here, we identified a novel function of caveolin-1 (Cav-1) in restraining Tfh cell motility, in which Icos transcription was repressed by peroxisome proliferator-activated receptor alpha (PPARα), unexpectedly, independence of lipid metabolism. In the context of autoimmunity, Cav-1 and PPARα expressions were decreased in CD4+ T cells from pSS patients and mice with experimental SS (ESS), while Cav-1 deficiency significantly exacerbated Tfh cell response and ESS pathology. Importantly, pharmaceutical activation of PPARα with fenofibrate effectively ameliorated ESS in mice with acute or chronic inflammation. These results revealed an unrecognized role of Cav-1/PPARα axis in Tfh cell tolerance, suggesting PPARα as a promising target in the treatment of humoral autoimmunity.
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Lin et al. (2023) studied this question.
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