PMID- 35597820
OWN - NLM
STAT- MEDLINE
DCOM- 20220524
LR  - 20230214
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 May 21
TI  - Bone marrow-derived macrophages from a murine model of Sjogren's syndrome 
      demonstrate an aberrant, inflammatory response to apoptotic cells.
PG  - 8593
LID - 10.1038/s41598-022-12608-4 [doi]
LID - 8593
AB  - Sjogren's syndrome (SjS) is a female-dominated autoimmune disease involving 
      lymphocytic infiltration of the exocrine glands. We have previously demonstrated 
      cleavage of the TAM (Tyro3, Axl, Mer) receptor Mer is enhanced in SjS, leading to 
      defective efferocytosis. Mer also plays a role in modulating phagocyte 
      inflammatory response to apoptotic cells. Here we investigated the SjS macrophage 
      response to apoptotic cells (AC). Bone marrow-derived macrophages (BMDMs) from 
      SjS-susceptible (SjS(s)) C57BL/6.NOD-Aec1Aec2 mice and C57BL/6 (B6) controls were 
      treated with either AC or CpG-oligodeoxynucleotides. RNA was collected from 
      macrophages and bulk sequencing was performed to analyze transcripts. Cytokine 
      expression was confirmed by Bio-plex. RT-qPCR was used to determine toll-like 
      receptor (TLR) 7 and 9 involvement in BMDM inflammatory response to apoptotic 
      cells. SjS(S) BMDMs exhibited a distinct transcriptional profile involving 
      upregulation of a broad array of inflammatory genes that were not elevated in B6 
      BMDMs by AC. Inhibition of TLR 7 and 9 was found to limit the inflammatory 
      response of SjS(S) BMDMs to ACs. ACs elicit an inflammatory reaction in SjS(S) 
      BMDMs distinct from that observed in B6 BMDMs. This discovery of aberrant 
      macrophage behavior in SjS in conjunction with previously described efferocytosis 
      defects suggests an expanded role for macrophages in SjS, where uncleared dead 
      cells stimulate an inflammatory response through macrophage TLRs recruiting 
      lymphocytes, participating in co-stimulation and establishing an environment 
      conducive to autoimmunity.
CI  - (c) 2022. The Author(s).
FAU - Witas, Richard
AU  - Witas R
AD  - Department of Infectious Diseases and Immunology, College of Veterinary Medicine, 
      University of Florida, PO Box 110880, Gainesville, FL, 32611-0880, USA.
AD  - Department of Oral Biology, College of Dentistry, University of Florida, 
      Gainesville, FL, USA.
FAU - Shen, Yiran
AU  - Shen Y
AD  - Department of Infectious Diseases and Immunology, College of Veterinary Medicine, 
      University of Florida, PO Box 110880, Gainesville, FL, 32611-0880, USA.
FAU - Nguyen, Cuong Q
AU  - Nguyen CQ
AD  - Department of Infectious Diseases and Immunology, College of Veterinary Medicine, 
      University of Florida, PO Box 110880, Gainesville, FL, 32611-0880, USA. 
      nguyenc@ufl.edu.
AD  - Department of Oral Biology, College of Dentistry, University of Florida, 
      Gainesville, FL, USA. nguyenc@ufl.edu.
AD  - Center of Orphaned Autoimmune Diseases, University of Florida, Gainesville, FL, 
      USA. nguyenc@ufl.edu.
LA  - eng
GR  - R01 DE028544/DE/NIDCR NIH HHS/United States
GR  - DE023433/NH/NIH HHS/United States
GR  - DE21990/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20220521
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Disease Models, Animal
MH  - Female
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred NOD
MH  - *Sjogren's Syndrome
PMC - PMC9124194
COIS- The authors declare no competing interests.
EDAT- 2022/05/22 06:00
MHDA- 2022/05/25 06:00
PMCR- 2022/05/21
CRDT- 2022/05/21 23:18
PHST- 2022/01/12 00:00 [received]
PHST- 2022/05/05 00:00 [accepted]
PHST- 2022/05/21 23:18 [entrez]
PHST- 2022/05/22 06:00 [pubmed]
PHST- 2022/05/25 06:00 [medline]
PHST- 2022/05/21 00:00 [pmc-release]
AID - 10.1038/s41598-022-12608-4 [pii]
AID - 12608 [pii]
AID - 10.1038/s41598-022-12608-4 [doi]
PST - epublish
SO  - Sci Rep. 2022 May 21;12(1):8593. doi: 10.1038/s41598-022-12608-4.