ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
TGFβ1 attenuates microglial IL1β release through inhibition of NLRP3 inflammasome priming
Provisionally accepted
- 1University of Rostock, Institute of Anatomy, Rostock, Germany
- 2Medical Faculty OWL, Anatomy and Cell Biology, Bielefeld University, Bielefeld, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Microglia reactivity has been described as a driver of brain tissue damage in multiple neurodegenerative pathologies. One of the key features of reactive microglia is the transcriptional upregulation of inflammatory markers, including components of the NLRP3 inflammasome such as Nlrp3, Casp1, and Il1b. The NLRP3 inflammasome is a multiprotein complex that plays an important role in several neurodegenerative diseases, being essential for cleavage and subsequent release of IL1β from activated microglia. Transforming growth factor β1 (TGFβ1) is a potent immunoregulatory cytokine with fundamental roles in microglial development, maintenance, and regulation of microglia reactivity. In the present study, we demonstrate that TGFβ1 is able to abrogate LPS-induced transcriptional upregulation of the inflammasome-associated genes Nlrp3, Casp1, and Il1b in BV2 cells as well as primary microglia. Moreover, we provide evidence that TGFβ1 treatment attenuates microglial IL1β release after nigericin-triggered NLRP3 inflammasome activation as a consequence of reduced priming. Finally, we demonstrate that silencing of microglial TGFβ signalling in vivo results in upregulation of Casp1, Il18, and Il1b. Together, our data enhance the understanding of how TGFβ1 and microglial TGFβ signaling regulate microglial reactivity, further highlighting the essential functions of TGFβ1 as a potent immunoregulatory factor for microglia.
Keywords: TGFβ1, Microglia, Inflammasome, NLRP3, IL1b, LPS
Received: 06 May 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 Kalischer, Potru, Lehmann, Jahn and Spittau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Björn Spittau
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.