PMID- 31755557 OWN - NLM STAT- MEDLINE DCOM- 20200427 LR - 20200427 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 159 IP - 3 DP - 2020 Mar TI - TRIM21 controls Toll-like receptor 2 responses in bone-marrow-derived macrophages. PG - 335-343 LID - 10.1111/imm.13157 [doi] AB - TRIM21 is an interferon-stimulated E3 ligase that controls the activity of pattern-recognition signaling via ubiquitination of interferon regulatory factors and DDX41. Previous studies on the role of TRIM21 in innate immune responses have yielded contradictory results, suggesting that the role of TRIM21 is cell specific. Here, we report that bone-marrow-derived macrophages (BMDMs) generated from Trim21(-/-) mice have reduced expression of mature macrophage markers. Reflecting their reduced differentiation in response to macrophage colony-stimulating factor (M-CSF), Trim21(-/-) BMDMs had decreased expression of M-CSF signature genes. Although Trim21(-/-) BMDMs responded normally to Toll-like receptor 9 (TLR9) activation, they produced lower levels of pro-inflammatory cytokines in response to the TLR2 agonist PAM3CSK4. In line with this, the response to infection with the Bacillus Calmette-Guerin strain of Mycobacterium bovis was also diminished in Trim21(-/-) BMDMs. Our results indicate that TRIM21 controls responses to TLR2 agonists. CI - (c) 2019 The Authors. Immunology published by John Wiley & Sons Ltd. FAU - Sjostrand, Maria AU - Sjostrand M AD - Unit of Rheumatology, Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. FAU - Carow, Berit AU - Carow B AD - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. FAU - Nyberg, William A AU - Nyberg WA AD - Unit of Rheumatology, Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. FAU - Covacu, Ruxandra AU - Covacu R AD - Unit of Neuroimmunology, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. FAU - Rottenberg, Martin E AU - Rottenberg ME AD - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. FAU - Espinosa, Alexander AU - Espinosa A AUID- ORCID: 0000-0003-1107-776X AD - Unit of Rheumatology, Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191212 PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Lipopeptides) RN - 0 (Pam(3)CSK(4) peptide) RN - 0 (Ribonucleoproteins) RN - 0 (SS-A antigen) RN - 0 (Tlr2 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Cell Differentiation MH - Cells, Cultured MH - Cytokines/*metabolism MH - Host-Pathogen Interactions MH - Inflammation Mediators/*metabolism MH - Lipopeptides/pharmacology MH - Macrophage Colony-Stimulating Factor/pharmacology MH - Macrophages/drug effects/immunology/*metabolism/microbiology MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mycobacterium bovis/immunology/pathogenicity MH - Phenotype MH - Ribonucleoproteins/deficiency/genetics/*metabolism MH - Signal Transduction MH - Toll-Like Receptor 2/agonists/genetics/*metabolism PMC - PMC7011629 OTO - NOTNLM OT - TRIM21 OT - Toll-like receptor 2 OT - macrophage EDAT- 2019/11/23 06:00 MHDA- 2020/04/28 06:00 PMCR- 2019/12/12 CRDT- 2019/11/23 06:00 PHST- 2019/02/13 00:00 [received] PHST- 2019/11/14 00:00 [revised] PHST- 2019/11/18 00:00 [accepted] PHST- 2019/11/23 06:00 [pubmed] PHST- 2020/04/28 06:00 [medline] PHST- 2019/11/23 06:00 [entrez] PHST- 2019/12/12 00:00 [pmc-release] AID - IMM13157 [pii] AID - 10.1111/imm.13157 [doi] PST - ppublish SO - Immunology. 2020 Mar;159(3):335-343. doi: 10.1111/imm.13157. Epub 2019 Dec 12.