PMID- 29777213
OWN - NLM
STAT- MEDLINE
DCOM- 20190422
LR  - 20211204
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Linking)
VI  - 19
IP  - 6
DP  - 2018 Jun
TI  - Semaphorin 6D reverse signaling controls macrophage lipid metabolism and 
      anti-inflammatory polarization.
PG  - 561-570
LID - 10.1038/s41590-018-0108-0 [doi]
AB  - Polarization of macrophages into pro-inflammatory or anti-inflammatory states has 
      distinct metabolic requirements, with mechanistic target of rapamycin (mTOR) 
      kinase signaling playing a critical role. However, it remains unclear how mTOR 
      regulates metabolic status to promote polarization of these cells. Here we show 
      that an mTOR-Semaphorin 6D (Sema6D)-Peroxisome proliferator receptor gamma (PPARgamma) 
      axis plays critical roles in macrophage polarization. Inhibition of mTOR or loss 
      of Sema6D blocked anti-inflammatory macrophage polarization, concomitant with 
      severe impairments in PPARgamma expression, uptake of fatty acids, and lipid 
      metabolic reprogramming. Macrophage expression of the receptor Plexin-A4 is 
      responsible for Sema6D-mediated anti-inflammatory polarization. We found that a 
      tyrosine kinase, c-Abl, which associates with the cytoplasmic region of Sema6D, 
      is required for PPARgamma expression. Furthermore, Sema6D is important for generation 
      of intestinal resident CX3CR1(hi) macrophages and prevents development of 
      colitis. Collectively, these findings highlight crucial roles for Sema6D reverse 
      signaling in macrophage polarization, coupling immunity, and metabolism via 
      PPARgamma.
FAU - Kang, Sujin
AU  - Kang S
AUID- ORCID: 0000-0001-5086-1405
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan. kang@imed3.med.osaka-u.ac.jp.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan. 
      kang@imed3.med.osaka-u.ac.jp.
AD  - Department of Immune Regulation, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan. kang@imed3.med.osaka-u.ac.jp.
FAU - Nakanishi, Yoshimitsu
AU  - Nakanishi Y
AUID- ORCID: 0000-0001-6172-6364
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan.
FAU - Kioi, Yoshiyuki
AU  - Kioi Y
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan.
FAU - Okuzaki, Daisuke
AU  - Okuzaki D
AUID- ORCID: 0000-0002-4552-783X
AD  - Genome Information Research Center, Research Institute for Microbial Diseases, 
      Osaka University, Suita City, Osaka, Japan.
FAU - Kimura, Tetsuya
AU  - Kimura T
AUID- ORCID: 0000-0001-6367-7818
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
FAU - Takamatsu, Hyota
AU  - Takamatsu H
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan.
FAU - Koyama, Shohei
AU  - Koyama S
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan.
FAU - Nojima, Satoshi
AU  - Nojima S
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Pathology, Graduate School of Medicine, Osaka University, Suita 
      City, Osaka, Japan.
FAU - Nishide, Masayuki
AU  - Nishide M
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan.
FAU - Hayama, Yoshitomo
AU  - Hayama Y
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan.
FAU - Kinehara, Yuhei
AU  - Kinehara Y
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan.
FAU - Kato, Yasuhiro
AU  - Kato Y
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan.
FAU - Nakatani, Takeshi
AU  - Nakatani T
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan.
FAU - Shimogori, Tomomi
AU  - Shimogori T
AD  - RIKEN Brain Science Institute, Laboratory for Molecular Mechanisms of Thalamus 
      Development, Saitama, Japan.
FAU - Takagi, Junichi
AU  - Takagi J
AD  - Laboratory of Protein Synthesis and Expression, Institute for Protein Research, 
      Osaka University, Suita City, Osaka, Japan.
FAU - Toyofuku, Toshihiko
AU  - Toyofuku T
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan.
AD  - Department of Immunology and Regenerative Medicine, Graduate School of Medicine, 
      Osaka University, Suita City, Osaka, Japan.
FAU - Kumanogoh, Atsushi
AU  - Kumanogoh A
AUID- ORCID: 0000-0003-4749-7117
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita City, Osaka, Japan. kumanogo@imed3.med.osaka-u.ac.jp.
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      medicine, Osaka University, Suita City, Osaka, Japan. 
      kumanogo@imed3.med.osaka-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180518
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (PPAR gamma)
RN  - 0 (Sema6d protein, mouse)
RN  - 0 (Semaphorins)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Nat Immunol. 2018 Jun;19(6):512-514. PMID: 29777214
MH  - Animals
MH  - Cell Differentiation/immunology
MH  - Colitis/immunology
MH  - Inflammation/immunology/*metabolism
MH  - Lipid Metabolism/*immunology
MH  - Macrophages/cytology/immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - PPAR gamma/immunology/*metabolism
MH  - Semaphorins/immunology/*metabolism
MH  - Signal Transduction/immunology
MH  - TOR Serine-Threonine Kinases/immunology/metabolism
EDAT- 2018/05/20 06:00
MHDA- 2019/04/23 06:00
CRDT- 2018/05/20 06:00
PHST- 2017/06/26 00:00 [received]
PHST- 2018/04/04 00:00 [accepted]
PHST- 2018/05/20 06:00 [pubmed]
PHST- 2019/04/23 06:00 [medline]
PHST- 2018/05/20 06:00 [entrez]
AID - 10.1038/s41590-018-0108-0 [pii]
AID - 10.1038/s41590-018-0108-0 [doi]
PST - ppublish
SO  - Nat Immunol. 2018 Jun;19(6):561-570. doi: 10.1038/s41590-018-0108-0. Epub 2018 
      May 18.