Files and links (2)
Published (Version of record)CC BY V4.0, Open Access
Published (Version of record)CC BY V4.0, Open
Journal article
Interleukin-38 is a negative regulator of trained immunity—A retrospective multi-omics study
iScience, Vol.28(11), pp.1-19
21/11/2025
PMID: 41280669
Metrics
1 Record Views
Abstract
Trained immunity is a long-lasting innate immune cell phenotype with benefits in infection control and recognized anti-cancer effects. Conversely, inappropriately induced trained immunity contributes to pathological inflammation, warranting the exploration of regulatory pathways. We explore interleukin-38 (IL-38) as a regulator of trained immunity in vivo in a cohort of 325 healthy adults vaccinated with Bacillus Calmette-Guérin (BCG). Using multi-omics profiling, we find that IL-38 is negatively associated with trained immunity on metabolic and epigenetic level. Genetic variants in IL1F10, encoding for IL-38, further link IL-38 to diminished training responses. These associations were validated in human and murine models. We confirmed that IL-38 functionally impairs anti-microbial traits of trained immunity in trained immunity-infection models in vivo (IL-38KO mice) and in vitro (human monocytes). Our study therefore suggests that IL-38 endogenously regulates the induction of trained immunity in humans in vivo.
Details
- Title
- Interleukin-38 is a negative regulator of trained immunity—A retrospective multi-omics study
- Creators
- Lisa U. Teufel - RUMCNVasiliki Matzaraki - RUMCNLukas Folkman - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)Dennis M. de Graaf - University of Colorado (USA)Rob ter Horst - CeMM Research Center for Molecular MedicineSimone J.C.F.M. Moorlag - RUMCNJéssica C. dos Santos - RUMCNCatharina M. Mulders-Manders - RUMCNThomas Krausgruber - CeMM Research Center for Molecular MedicineCharles Dinarello - University of Colorado (USA, Colorado)Mihai G. Netea - RUMCNLeo A.B. Joosten - RUMCNRob J.W. Arts - RUMCN
- Publication Details
- iScience, Vol.28(11), pp.1-19
- Publisher
- Elsevier Inc
- Grant note
- VENI grant: 09150161810007 European Research Council (ERC): 833247 Marie Sklodowska-Curie Actions Individual Fellowship: 842480 EMBO Postdoctoral Fellowship: ALTF 702-2020 NIH: AI15614 Marie Curie Actions (MSCA): 842480
The authors would like to thank all participating patients and volunteers of the 300BCG and the 20BCG cohorts for their participation. We further thank Profa. Dra. Fatima Ribeiro-Dias (Laboratorio de Imunidade Natural [LIN], Instituto de Patologia Tropical e Saude Publica, Universidade Federal de Goias, Goiania, Goias, Brazil) for kindly providing the Leishmania spp. and Christoph Bock (Medical University of Vienna, Institute of Artificial Intelligence, Center for Medical Data Science, Austria & CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria) for his support in writing the manuscript. R.J.W.A. is supported by the VENI grant (09150161810007). M.G.N. is supported by an Advanced grant of the European Research Council (ERC, #833247). L.F. was supported by a Marie Sklodowska-Curie Actions Individual Fellowship (grant agreement no. 842480). R.t.H. was supported by an EMBO Postdoctoral Fellowship (grant agreement no. ALTF 702-2020). C.D. is supported by the NIH grant AI15614.
- Identifiers
- 991013341144702368
- Copyright
- © 2025 The Author(s).
- Academic Unit
- Faculty of Science and Engineering
- Language
- English
- Resource Type
- Journal article