Tim-3 protects decidual stromal cells from toll-like receptor-mediated apoptosis and inflammatory reactions and promotes Th2 bias at the maternal-fetal interface

Scientific Reports
Song-Cun WangMei-Rong Du

Abstract

Toll-like receptors (TLRs) are important in mediating immune responses against various pathogens during pregnancy. However, uncontrolled TLR-triggered inflammation will endanger normal pregnancy, resulting in pregnancy loss. Therefore, maintenance of a moderate inflammatory response is crucial for successful pregnancy under conditions of infection. Here, we demonstrated significantly lowered expression of T-cell immunoglobulin and mucin domain 3 (Tim-3) in miscarried decidual stromal cells (DSCs), indicating that Tim-3 might play important roles in maintaining successful pregnancies. Activation of TLR signaling induced pro-inflammatory cytokine production and apoptosis of DSCs, which was accompanied by up-regulated Tim-3 expression. Tim-3, in turn, protected DSCs from TLR-mediated apoptosis in an ERK1/2 pathway-dependent manner. In addition, Tim-3 inhibited TLR signaling-induced inflammatory cytokine production by DSCs through suppressing NF-κB activation. Tim-3 increased production of T helper 2 (Th2)-type cytokines by DSCs and reversed the inhibitory effect of LPS on Th2 cytokine generation by up-regulation of interferon regulatory factor 4 expression. Tim-3 blockade abolished the effect of Tim-3 on the inflammatory response ...Continue Reading

References

Oct 14, 2005·The Journal of Biological Chemistry·Ryuichi MashimaAkihiko Yoshimura
Dec 24, 2005·Journal of Thrombosis and Haemostasis : JTH·E M EgorinaB Østerud
Feb 25, 2006·Cell·Shizuo AkiraOsamu Takeuchi
May 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sylvia Frisancho-KissDelisa Fairweather
Oct 24, 2007·Human Reproduction·Osmany BlancoEnrique G Olivares
Nov 6, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Raj Raghupathy, Jaroslaw Kalinka
Aug 22, 2008·Immunological Investigations·Vikki M Abrahams
Sep 12, 2008·Journal of Leukocyte Biology·Maaike S M van MourikCobi J Heijnen
May 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jie ZhaoBo Huang
Jun 30, 2009·Journal of Reproductive Immunology·Yi LinShigeru Saito
Jun 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica E ThaxtonSurendra Sharma
Jun 12, 2010·Immunological Reviews·Gordon J FreemanRosemarie H DeKruyff
Oct 29, 2010·The New England Journal of Medicine·D Ware BranchRobert M Silver
Dec 29, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen J RenaudCharles H Graham
Mar 10, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Astrid FriebePetra C Arck
May 20, 2011·Biology of Reproduction·Mukesh Kumar JaiswalKenneth D Beaman
Jul 19, 2011·Nature Medicine·Shokrollah ElahiHelen Horton
Mar 1, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Rodrigo LiberalMaria Serena Longhi
Mar 3, 2012·American Journal of Reproductive Immunology : AJRI·Leif MatthiesenSurendra Sharma
Oct 23, 2012·Cancer Metastasis Reviews·Cindy NeuzilletEric Raymond
Feb 1, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaomei YangGencheng Han
Apr 5, 2013·PLoS Pathogens·Judith LeitnerPeter Steinberger
Apr 24, 2014·American Journal of Reproductive Immunology : AJRI·Kaori KogaYutaka Osuga
May 2, 2014·European Journal of Immunology·Magdalena Huber, Michael Lohoff

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Citations

Feb 20, 2016·American Journal of Reproductive Immunology : AJRI·Qian LiuJing Yang
May 20, 2015·Immunology Letters·Paola VaccaMaria Cristina Mingari
Sep 8, 2015·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Haiyan HaoDongrui Deng
Oct 30, 2016·Journal of Reproductive Immunology·Xiao-Hui HuAi-Hua Liao
May 4, 2017·American Journal of Reproductive Immunology : AJRI·Stella LiongMartha Lappas
Oct 31, 2017·American Journal of Reproductive Immunology : AJRI·Fanfan LiDongrui Deng
Nov 25, 2018·Parasite Immunology·Margarida BorgesCraig W Roberts
May 7, 2019·Frontiers in Immunology·Eva MikoLaszlo Szereday
Jul 7, 2020·Frontiers in Physiology·Justin G PadronClaire E Kendal-Wright
Mar 21, 2018·Frontiers of Medicine·Xuezhou YangHui Xing
Jun 17, 2021·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Yihong ChenShan Zheng
Jul 26, 2021·International Immunopharmacology·Leila Mohamed KhosroshahiLeili Aghebati-Maleki
Oct 29, 2021·Journal of Cellular and Molecular Medicine·Wen-Xuan LiLi-Ping Jin
Jul 8, 2021·Reproductive Sciences·Songcun WangYing Zhang

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Methods Mentioned

BETA
PCR
flow cytometry
Infrared Imaging

Software Mentioned

Prism
GraphPad
FlowJo

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis