PMID- 33552047
OWN - NLM
STAT- MEDLINE
DCOM- 20210614
LR  - 20231110
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Tropomodulin1 Expression Increases Upon Maturation in Dendritic Cells and 
      Promotes Their Maturation and Immune Functions.
PG  - 587441
LID - 10.3389/fimmu.2020.587441 [doi]
LID - 587441
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells. Upon 
      maturation, DCs express costimulatory molecules and migrate to the lymph nodes to 
      present antigens to T cells. The actin cytoskeleton plays key roles in multiple 
      aspects of DC functions. However, little is known about the mechanisms and 
      identities of actin-binding proteins that control DC maturation and 
      maturation-associated functional changes. Tropomodulin1 (Tmod1), an actin-capping 
      protein, controls actin depolymerization and nucleation. We found that Tmod1 was 
      expressed in bone marrow-derived immature DCs and was significantly upregulated 
      upon lipopolysaccharide (LPS)-induced DC maturation. By characterizing 
      LPS-induced mature DCs (mDCs) from Tmod1 knockout mice, we found that compared 
      with Tmod1(+/+) mDCs, Tmod1-deficient mDCs exhibited lower surface expression of 
      costimulatory molecules and chemokine receptors and reduced secretion of 
      inflammatory cytokines, suggesting that Tmod1 deficiency retarded DC maturation. 
      Tmod1-deficient mDCs also showed impaired random and chemotactic migration, 
      deteriorated T-cell stimulatory ability, and reduced F-actin content and cell 
      stiffness. Furthermore, Tmod1-deficient mDCs secreted high levels of IFN-beta and 
      IL-10 and induced immune tolerance in an experimental autoimmune 
      encephalomyelitis (EAE) mouse model. Mechanistically, Tmod1 deficiency affected 
      TLR4 signaling transduction, resulting in the decreased activity of 
      MyD88-dependent NFkappaB and MAPK pathways but the increased activity of the 
      TRIF/IRF3 pathway. Rescue with exogenous Tmod1 reversed the effect of Tmod1 
      deficiency on TLR4 signaling. Therefore, Tmod1 is critical in regulating DC 
      maturation and immune functions by regulating TLR4 signaling and the actin 
      cytoskeleton. Tmod1 may be a potential target for modulating DC functions, a 
      strategy that would be beneficial for immunotherapy for several diseases.
CI  - Copyright (c) 2021 Liu, Xia, Wang, Zhou, Sung, Long, Geng, Zeng and Yao.
FAU - Liu, Xianmei
AU  - Liu X
AD  - School of Basic Medical Sciences, School of Biology and Engineering, Guizhou 
      Medical University, Guiyang, China.
AD  - Hemorheology Center, Department of Physiology and Pathophysiology, School of 
      Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
FAU - Xia, Xue
AU  - Xia X
AD  - School of Basic Medical Sciences, School of Biology and Engineering, Guizhou 
      Medical University, Guiyang, China.
AD  - Hemorheology Center, Department of Physiology and Pathophysiology, School of 
      Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
FAU - Wang, Xifu
AU  - Wang X
AD  - Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, 
      Beijing, China.
FAU - Zhou, Jing
AU  - Zhou J
AD  - Hemorheology Center, Department of Physiology and Pathophysiology, School of 
      Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
FAU - Sung, Lanping Amy
AU  - Sung LA
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, CA, 
      United States.
FAU - Long, Jinhua
AU  - Long J
AD  - School of Basic Medical Sciences, School of Biology and Engineering, Guizhou 
      Medical University, Guiyang, China.
FAU - Geng, Xueyu
AU  - Geng X
AD  - Hemorheology Center, Department of Physiology and Pathophysiology, School of 
      Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
FAU - Zeng, Zhu
AU  - Zeng Z
AD  - School of Basic Medical Sciences, School of Biology and Engineering, Guizhou 
      Medical University, Guiyang, China.
FAU - Yao, Weijuan
AU  - Yao W
AD  - Hemorheology Center, Department of Physiology and Pathophysiology, School of 
      Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
AD  - Department of Integration of Chinese and Western Medicine, School of Basic 
      Medical Science, Peking University Health Center, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210115
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Tmod1 protein, mouse)
RN  - 0 (Tropomodulin)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/immunology
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Encephalomyelitis, Autoimmune, Experimental/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Signal Transduction/immunology
MH  - Tropomodulin/*immunology/*metabolism
PMC - PMC7856346
OTO - NOTNLM
OT  - TLR4 signaling
OT  - Tmod1
OT  - antigen presentation
OT  - dendritic cells
OT  - maturation
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/02/09 06:00
MHDA- 2021/06/16 06:00
PMCR- 2020/01/01
CRDT- 2021/02/08 05:36
PHST- 2020/07/26 00:00 [received]
PHST- 2020/12/03 00:00 [accepted]
PHST- 2021/02/08 05:36 [entrez]
PHST- 2021/02/09 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.587441 [doi]
PST - epublish
SO  - Front Immunol. 2021 Jan 15;11:587441. doi: 10.3389/fimmu.2020.587441. eCollection 
      2020.