| Title: |
Interleukin-38 is a negative regulator of trained immunity—A retrospective multi-omics study |
| Authors: |
Teufel, LU; Matzaraki, V; Folkman, L; de Graaf, DM; Horst, RT; Moorlag, SJCFM; dos Santos, JC; Mulders-Manders, CM; Krausgruber, T; Dinarello, C; Netea, MG; Joosten, LAB; Arts, RJW |
| Publisher Information: |
Elsevier |
| Publication Year: |
2025 |
| Collection: |
Griffith University: Griffith Research Online |
| Subject Terms: |
Immunology; Biomedical and clinical sciences |
| Description: |
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. ; Full Text |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
iScience; Teufel, LU; Matzaraki, V; Folkman, L; de Graaf, DM; Horst, RT; Moorlag, SJCFM; dos Santos, JC; Mulders-Manders, CM; Krausgruber, T; Dinarello, C; Netea, MG; Joosten, LAB; Arts, RJW, Interleukin-38 is a negative regulator of trained immunity—A retrospective multi-omics study, iScience, 2025, 28 (11), pp. 113758; https://hdl.handle.net/10072/440189 |
| DOI: |
10.1016/j.isci.2025.113758 |
| Availability: |
https://hdl.handle.net/10072/440189; https://doi.org/10.1016/j.isci.2025.113758 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; © 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). ; open access |
| Accession Number: |
edsbas.AAF05761 |
| Database: |
BASE |