Increased expression of surface CD44 in hypoxia-DCs skews helper T cells toward a Th2 polarization

Scientific Reports
Meixiang YangXun Qu

Abstract

A low partial oxygen pressure (hypoxia) occurs in many pathological environments, such as solid tumors and inflammatory lesions. Understanding the cellular response to hypoxic stress has broad implications for human diseases. As we previously reported, hypoxia significantly altered dendritic cells (DCs) to a DC2 phenotype and promoted a Th2 polarization of naïve T cells with increased IL-4 production. However, the underlying mechanisms still remain largely unknown. In this study, we found the over-expression of surface CD44 in DCs was involved in this process via ligand binding. Further investigation showed hypoxia could reduce the surface expression of membrane type 1 metalloprotease (MT1-MMP) via down-regulating the kinesin-like protein KIF2A, which subsequently alleviated the shedding of CD44 from DCs. Moreover, KIF2A expression was found negatively regulated by HIF-1α in hypoxic microenvironment. These results suggest a previously uncharacterized mechanism by which hypoxia regulates the function of DCs via KIF2A/MT1-MMP/CD44 axis, providing critical information to understand the immune response under hypoxia.

References

Sep 1, 1996·The Journal of Experimental Medicine·Y GuoY Liu
Jan 1, 1997·Advances in Experimental Medicine and Biology·H Haegel-KronenbergerD Hanau
Sep 3, 1998·The Journal of Clinical Investigation·J MollP Herrlich
Jun 3, 2000·Annual Review of Immunology·J BanchereauK Palucka
May 31, 2001·The Journal of Cell Biology·M KajitaM Seiki
Jan 10, 2002·Biochemical and Biophysical Research Communications·Zhuang ChenJim Xiang
Feb 13, 2002·The American Journal of Pathology·Isamu OkamotoAlbert J Wong
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Katrina GeeAshok Kumar
Jan 4, 2003·Nature Reviews. Molecular Cell Biology·Helmut PontaPeter A Herrlich
Jul 23, 2003·Current Pharmaceutical Design·Hidefumi KojimaMarilia Cascalho
Dec 2, 2004·Expert Opinion on Biological Therapy·Ronald B MossDennis J Carlo
Dec 15, 2004·Cancer Science·Osamu Nagano, Hideyuki Saya
Dec 21, 2004·Springer Seminars in Immunopathology·Esther C de JongMartien L Kapsenberg
Mar 15, 2005·Current Opinion in Allergy and Clinical Immunology·P Ly NgocJuan C Celedón
Feb 9, 2008·Cell Death and Differentiation·A Weidemann, R S Johnson
Mar 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jonathan JantschCarsten Willam
Apr 5, 2008·Journal of Leukocyte Biology·Venkatesh L HegdeMitzi Nagarkatti
Aug 13, 2008·Blood·Alessandra MancinoAntonio Sica
Mar 3, 2009·Vitamins and Hormones·Alexei Y Savinov, Alex Y Strongin
Mar 7, 2009·Acta Physiologica Hungarica·J M AdamsZ H Németh
Oct 1, 2009·Cancer Research·Sarmishtha DeGeorge R Stark
Feb 6, 2010·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Maira Cegatti BossetoSelma Giorgio
Aug 17, 2010·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jie GaoChangjun Zhu
Feb 18, 2011·The New England Journal of Medicine·Holger K Eltzschig, Peter Carmeliet
May 25, 2011·Nature Reviews. Cancer·William R Wilson, Michael P Hay
May 9, 2012·The EMBO Journal·Samantha N GreerMichael Ohh
Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Eric T ClambeyHolger K Eltzschig

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Citations

Mar 29, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Abraham J Al-AhmadEric V Shusta
Apr 2, 2019·Clinical and Translational Medicine·S K DanielV G Pillarisetty
Jun 7, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shan ZhuJingtao Chen
Jul 3, 2021·Cancers·Yuqing ZhangRolf A Brekken

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Methods Mentioned

BETA
PCR
ELISA
immunoprecipitations
co-immunoprecipitation
FACS
flow cytometry
transfection

Software Mentioned

LightCycler
Image J
Genchip Microarray Suite
CellQuest

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