PMID- 32269165
OWN - NLM
STAT- MEDLINE
DCOM- 20210623
LR  - 20220313
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Print)
IS  - 1946-6234 (Linking)
VI  - 12
IP  - 538
DP  - 2020 Apr 8
TI  - Kidney tissue hypoxia dictates T cell-mediated injury in murine lupus nephritis.
LID - 10.1126/scitranslmed.aay1620 [doi]
LID - eaay1620
AB  - The kidney is a frequent target of autoimmune injury, including in systemic lupus 
      erythematosus; however, how immune cells adapt to kidney's unique environment and 
      contribute to tissue damage is unknown. We found that renal tissue, which 
      normally has low oxygen tension, becomes more hypoxic in lupus nephritis. In the 
      injured mouse tissue, renal-infiltrating CD4(+) and CD8(+) T cells express 
      hypoxia-inducible factor-1 (HIF-1), which alters their cellular metabolism and 
      prevents their apoptosis in hypoxia. HIF-1-dependent gene-regulated pathways were 
      also up-regulated in renal-infiltrating T cells in human lupus nephritis. 
      Perturbation of these environmental adaptations by selective HIF-1 blockade 
      inhibited infiltrating T cells and reversed tissue hypoxia and injury in murine 
      models of lupus. The results suggest that targeting HIF-1 might be effective for 
      treating renal injury in autoimmune diseases.
CI  - Copyright (c) 2020 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Chen, Ping-Min
AU  - Chen PM
AUID- ORCID: 0000-0001-6532-4549
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Wilson, Parker C
AU  - Wilson PC
AUID- ORCID: 0000-0001-8647-9662
AD  - Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, 
      USA.
FAU - Shyer, Justin A
AU  - Shyer JA
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Veselits, Margaret
AU  - Veselits M
AUID- ORCID: 0000-0001-8755-6260
AD  - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, 
      Departments of Medicine and Pathology, University of Chicago, Chicago, IL 60637, 
      USA.
FAU - Steach, Holly R
AU  - Steach HR
AUID- ORCID: 0000-0003-0018-3129
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Cui, Can
AU  - Cui C
AUID- ORCID: 0000-0003-4736-4330
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Moeckel, Gilbert
AU  - Moeckel G
AD  - Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, 
      USA.
FAU - Clark, Marcus R
AU  - Clark MR
AD  - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, 
      Departments of Medicine and Pathology, University of Chicago, Chicago, IL 60637, 
      USA.
FAU - Craft, Joe
AU  - Craft J
AUID- ORCID: 0000-0002-1368-6756
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA. joseph.craft@yale.edu.
AD  - Department of Internal Medicine (Rheumatology, Allergy and Immunology), Yale 
      University School of Medicine, New Haven, CT 06520, USA.
LA  - eng
GR  - R37 AR040072/AR/NIAMS NIH HHS/United States
GR  - R01 AI152443/AI/NIAID NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - U19 AI082724/AI/NIAID NIH HHS/United States
GR  - R21 AI142145/AI/NIAID NIH HHS/United States
GR  - R01 AR074545/AR/NIAMS NIH HHS/United States
GR  - R01 AR040072/AR/NIAMS NIH HHS/United States
GR  - P30 DK079310/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
SB  - IM
CIN - Nat Rev Rheumatol. 2020 Jun;16(6):295. PMID: 32376996
CIN - Kidney Int. 2020 Oct;98(4):821-823. PMID: 32599087
MH  - Animals
MH  - CD8-Positive T-Lymphocytes
MH  - Hypoxia
MH  - Kidney
MH  - *Lupus Erythematosus, Systemic
MH  - *Lupus Nephritis
MH  - Mice
PMC - PMC8055156
MID - NIHMS1691877
COIS- Competing Interests: J.C. received research funding from AbbVie which was used to 
      partially support this work.
EDAT- 2020/04/10 06:00
MHDA- 2021/06/24 06:00
PMCR- 2021/04/19
CRDT- 2020/04/10 06:00
PHST- 2019/05/24 00:00 [received]
PHST- 2019/11/06 00:00 [revised]
PHST- 2020/02/28 00:00 [accepted]
PHST- 2020/04/10 06:00 [entrez]
PHST- 2020/04/10 06:00 [pubmed]
PHST- 2021/06/24 06:00 [medline]
PHST- 2021/04/19 00:00 [pmc-release]
AID - 12/538/eaay1620 [pii]
AID - 10.1126/scitranslmed.aay1620 [doi]
PST - ppublish
SO  - Sci Transl Med. 2020 Apr 8;12(538):eaay1620. doi: 10.1126/scitranslmed.aay1620.