PMID- 31720043 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200929 IS - 1598-2629 (Print) IS - 2092-6685 (Electronic) IS - 1598-2629 (Linking) VI - 19 IP - 5 DP - 2019 Oct TI - Ubiquitin E3 Ligase Pellino-1 Inhibits IL-10-mediated M2c Polarization of Macrophages, Thereby Suppressing Tumor Growth. PG - e32 LID - 10.4110/in.2019.19.e32 [doi] LID - e32 AB - Pellino-1 is a ubiquitin (Ub) E3 ligase that plays a role in M1, but not M2a polarization of macrophages. However, it is unknown whether Pellino-1 regulates IL-10-mediated M2c polarization of macrophages. Here, we found that Pellino-1 attenuated tumor growth by inhibiting M2c polarization of macrophages. Upon IL-10 stimulation, Pellino-1-deificient bone marrow-derived macrophages (BMDMs) showed higher expression of M2c markers, but not M2a, and M2b markers than wild-type (WT) BMDMs, indicating that Pellino-1 inhibits M2c polarization of macrophages. Pellino-1-deficient BMDMs exhibited a defect in mitochondria respiration, but enhancement of glycolysis during M2c polarization. During M2c polarization of macrophages, Pellino-1 increased STAT1 phosphorylation via K63-linked ubiquitination of IL-1 receptor associated kinase 1 (IRAK1). Furthermore, Lysm-CrePellino-1 (fl/fl) mice showed enhancement of tumor growth via regulating M2c polarization of tumor-associated macrophages. These results demonstrate that Pellino-1 inhibits IL-10-induced M2c macrophage polarization via K63-linked ubiquitination of IRAK1 and activation of STAT1, thereby inhibiting tumor growth in vivo. CI - Copyright (c) 2019. The Korean Association of Immunologists. FAU - Kim, Donghyun AU - Kim D AUID- ORCID: 0000-0001-7863-7384 AD - Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. FAU - Koh, Jaemoon AU - Koh J AUID- ORCID: 0000-0002-2824-5080 AD - Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea. FAU - Ko, Jae Sung AU - Ko JS AUID- ORCID: 0000-0003-3195-5910 AD - Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. FAU - Kim, Hye Young AU - Kim HY AUID- ORCID: 0000-0001-5978-512X AD - Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. FAU - Lee, Ho AU - Lee H AD - Graduate School of Cancer Science and Policy, Research Institute, National Cancer Center, Goyang 10408, Korea. FAU - Chung, Doo Hyun AU - Chung DH AUID- ORCID: 0000-0002-9948-8485 AD - Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. AD - Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea. LA - eng PT - Journal Article DEP - 20191017 PL - Korea (South) TA - Immune Netw JT - Immune network JID - 101137270 PMC - PMC6829073 OTO - NOTNLM OT - E3 ligase OT - M2c OT - Macrophages OT - Pellino-1 OT - Polarization OT - Tumors COIS- Conflict of Interest: The authors declare no potential conflicts of interest. EDAT- 2019/11/14 06:00 MHDA- 2019/11/14 06:01 PMCR- 2019/10/01 CRDT- 2019/11/14 06:00 PHST- 2019/08/26 00:00 [received] PHST- 2019/10/01 00:00 [revised] PHST- 2019/10/02 00:00 [accepted] PHST- 2019/11/14 06:00 [entrez] PHST- 2019/11/14 06:00 [pubmed] PHST- 2019/11/14 06:01 [medline] PHST- 2019/10/01 00:00 [pmc-release] AID - 2019190503 [pii] AID - 10.4110/in.2019.19.e32 [doi] PST - epublish SO - Immune Netw. 2019 Oct 17;19(5):e32. doi: 10.4110/in.2019.19.e32. eCollection 2019 Oct.