PMID- 35246034
OWN - NLM
STAT- MEDLINE
DCOM- 20220509
LR  - 20221021
IS  - 1471-2172 (Electronic)
IS  - 1471-2172 (Linking)
VI  - 23
IP  - 1
DP  - 2022 Mar 4
TI  - ERAP1 is a critical regulator of inflammasome-mediated proinflammatory and ER 
      stress responses.
PG  - 9
LID - 10.1186/s12865-022-00481-9 [doi]
LID - 9
AB  - BACKGROUND: In addition to its role in antigen presentation, recent reports 
      establish a new role for endoplasmic reticulum aminopeptidase 1 (ERAP1) in innate 
      immunity; however, the mechanisms underlying these functions are not fully 
      defined. We previously confirmed that loss of ERAP1 functions resulted in 
      exaggerated innate immune responses in a murine in vivo model. Here, we 
      investigated the role of ERAP1 in suppressing inflammasome pathways and their 
      dependence on ER stress responses. RESULTS: Using bone marrow-derived macrophages 
      (BMDMs), we found that loss of ERAP1 in macrophages resulted in exaggerated 
      production of IL-1beta and IL-18 and augmented caspase-1 activity, relative to wild 
      type macrophages. Moreover, an in vivo colitis model utilizing dextran sodium 
      sulfate (DSS) confirmed increased levels of proinflammatory cytokines and 
      chemokines in the colon of DSS treated ERAP1(-/-) mice as compared to identically 
      stimulated WT mice. Interestingly, stimulated ERAP1(-/-) BMDMs and CD4(+) T cells 
      simultaneously demonstrated exaggerated ER stress, assessed by increased 
      expression of ER stress-associated genes, a state that could be reverted to WT 
      levels with use of the ER stress inhibitor Tauroursodeoxycholic acid (TUDCA). 
      CONCLUSIONS: Together, these results not only suggest that ERAP1 is important for 
      regulating inflammasome dependent innate immune response pathways in vivo, but 
      also propose a mechanism that underlies these changes, that may be associated 
      with increased ER stress due to lack of normal ERAP1 functions.
CI  - (c) 2022. The Author(s).
FAU - Blake, Maja K
AU  - Blake MK
AD  - Department of Microbiology and Molecular Genetics, College of Osteopathic 
      Medicine, Michigan State University, East Lansing, MI, USA.
FAU - O'Connell, Patrick
AU  - O'Connell P
AD  - Department of Microbiology and Molecular Genetics, College of Osteopathic 
      Medicine, Michigan State University, East Lansing, MI, USA.
FAU - Pepelyayeva, Yuliya
AU  - Pepelyayeva Y
AD  - Department of Microbiology and Molecular Genetics, College of Osteopathic 
      Medicine, Michigan State University, East Lansing, MI, USA.
FAU - Godbehere, Sarah
AU  - Godbehere S
AD  - Department of Microbiology and Molecular Genetics, College of Osteopathic 
      Medicine, Michigan State University, East Lansing, MI, USA.
FAU - Aldhamen, Yasser A
AU  - Aldhamen YA
AD  - Department of Microbiology and Molecular Genetics, College of Osteopathic 
      Medicine, Michigan State University, East Lansing, MI, USA.
FAU - Amalfitano, Andrea
AU  - Amalfitano A
AD  - Department of Microbiology and Molecular Genetics, College of Osteopathic 
      Medicine, Michigan State University, East Lansing, MI, USA. amalfit1@msu.edu.
AD  - Department of Pediatrics, College of Osteopathic Medicine, Michigan State 
      University, East Lansing, MI, USA. amalfit1@msu.edu.
LA  - eng
GR  - R01 AR056981/AR/NIAMS NIH HHS/United States
GR  - T32 GM142521/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220304
PL  - England
TA  - BMC Immunol
JT  - BMC immunology
JID - 100966980
RN  - 0 (Inflammasomes)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - EC 3.4.11.- (Aminopeptidases)
RN  - EC 3.4.11.- (ERAP1 protein, mouse)
SB  - IM
MH  - *Aminopeptidases/genetics/metabolism
MH  - Animals
MH  - *Endoplasmic Reticulum Stress
MH  - Immunity, Innate/genetics
MH  - *Inflammasomes
MH  - Mice
MH  - Mice, Knockout
MH  - Minor Histocompatibility Antigens/genetics
PMC - PMC8895631
OTO - NOTNLM
OT  - Ankylosing spondylitis
OT  - ER stress
OT  - Inflammasome
OT  - Innate immunity
COIS- The authors have no financial competing interests.
EDAT- 2022/03/06 06:00
MHDA- 2022/05/10 06:00
PMCR- 2022/03/04
CRDT- 2022/03/05 05:24
PHST- 2021/11/29 00:00 [received]
PHST- 2022/02/08 00:00 [accepted]
PHST- 2022/03/05 05:24 [entrez]
PHST- 2022/03/06 06:00 [pubmed]
PHST- 2022/05/10 06:00 [medline]
PHST- 2022/03/04 00:00 [pmc-release]
AID - 10.1186/s12865-022-00481-9 [pii]
AID - 481 [pii]
AID - 10.1186/s12865-022-00481-9 [doi]
PST - epublish
SO  - BMC Immunol. 2022 Mar 4;23(1):9. doi: 10.1186/s12865-022-00481-9.