PMID- 38447248
OWN - NLM
STAT- Publisher
LR  - 20240306
IS  - 1095-9157 (Electronic)
IS  - 0896-8411 (Linking)
VI  - 145
DP  - 2024 Mar 5
TI  - CADHERIN-11 regulation of myeloid phagocytes and autoimmune inflammation in 
      murine lupus.
PG  - 103197
LID - S0896-8411(24)00031-3 [pii]
LID - 10.1016/j.jaut.2024.103197 [doi]
AB  - BACKGROUND AND OBJECTIVE: Understanding the regulation of efferocytosis by 
      myeloid phagocytes is important in identifying novel targets in systemic lupus 
      erythematosus (SLE). Cadherin-11 (CDH11), a cell adhesion molecule, is implicated 
      in inflammatory arthritis and fibrosis and recently been shown to regulate 
      macrophage phagocytosis. The extent and mechanism of this regulation is unknown. 
      Our objective was to examine the extent to which CDH11 regulates myeloid 
      phagocytes and contributes to autoimmunity and tissue inflammation. METHODS: We 
      analyzed efferocytosis in macrophages and dendritic cells (DCs) from WT and 
      Cdh11(-/-) mice and investigated the mechanisms in vitro. We investigated the 
      role of CDH11 in disease development in vivo using the pristane induced lupus 
      model. To translate the clinical relevance of CDH11 in human disease, we measured 
      serum CDH11 levels in two independent pediatric SLE (pSLE) cohorts and healthy 
      controls. RESULTS: Using bone marrow derived macrophages (BMDMs) and DCs (BMDCs), 
      we found impaired efferocytosis in phagocytes from Cdh11(-/-) mice, mediated by 
      downregulated efferocytosis receptor expression and RhoGTPase activation. 
      Specifically, loss of CDH11 downregulated Mertk expression and Rac1 activation in 
      BMDMs, and integrin alphaVbeta3 expression and Cdc42 activation in BMDCs, highlighting 
      distinct pathways. In vivo, Cdh11-/- mice displayed defective efferocytosis and 
      increased accumulation of apoptotic debris in pristane-induced lupus. Further, 
      Cdh11-/- mice had enhanced systemic inflammation and autoimmune inflammation with 
      increased anti-dsDNA autoantibodies, splenomegaly, type I interferons, and 
      inflammatory cytokines. Paradoxically, at the tissue level, Cdh11-/- mice were 
      protected against glomerulonephritis, indicating a dual role in murine lupus. 
      Finally, SLE patients had increased serum CDH11 compared to controls. CONCLUSION: 
      This study highlights a novel role of CDH11 in regulating myeloid cells and 
      efferocytosis and its potential as a contributor to development in autoimmunity 
      murine lupus. Despite the increase in autoimmunity, Cdh11(-/-) mice developed 
      decreased tissue inflammation and damage.
CI  - Copyright (c) 2024. Published by Elsevier Ltd.
FAU - Chavula, Thandiwe
AU  - Chavula T
AD  - Section of Immunology, Allergy and Rheumatology, Department of Medicine, Baylor 
      College of Medicine, Houston, TX, USA.
FAU - To, Sarah
AU  - To S
AD  - Section of Immunology, Allergy and Rheumatology, Department of Medicine, Baylor 
      College of Medicine, Houston, TX, USA.
FAU - Smith, Jennifer
AU  - Smith J
AD  - Section of Immunology, Allergy and Rheumatology, Department of Medicine, Baylor 
      College of Medicine, Houston, TX, USA.
FAU - Pedroza, Mesias
AU  - Pedroza M
AD  - Section of Immunology, Allergy and Rheumatology, Department of Medicine, Baylor 
      College of Medicine, Houston, TX, USA.
FAU - Nimri, Jena
AU  - Nimri J
AD  - Section of Immunology, Allergy and Rheumatology, Department of Medicine, Baylor 
      College of Medicine, Houston, TX, USA.
FAU - Devaraj, Sridevi
AU  - Devaraj S
AD  - Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, 
      USA; Pathology Department, Texas Children's Hospital, Houston, TX, USA.
FAU - Wenderfer, Scott
AU  - Wenderfer S
AD  - Department of Pediatric Nephrology, B.C. Children's Hospital, Vancouver, BC, 
      Canada.
FAU - Vogel, Tiphanie P
AU  - Vogel TP
AD  - Section of Immunology, Allergy and Rheumatology, Department of Medicine, Baylor 
      College of Medicine, Houston, TX, USA; Department of Pediatrics-Rheumatology, 
      Baylor College of Medicine, Houston, TX, USA; Division of Rheumatology, Texas 
      Children's Hospital, Houston, TX, USA.
FAU - Agarwal, Sandeep K
AU  - Agarwal SK
AD  - Section of Immunology, Allergy and Rheumatology, Department of Medicine, Baylor 
      College of Medicine, Houston, TX, USA. Electronic address: skagarwa@bcm.edu.
LA  - eng
PT  - Journal Article
DEP - 20240305
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
SB  - IM
OTO - NOTNLM
OT  - Autoimmunity
OT  - Cadherin-11
OT  - Efferocytosis
OT  - Myeloid cells
OT  - Pristane lupus
COIS- Declaration of competing interest The authors declare that no potential conflicts 
      of interest exist.
EDAT- 2024/03/07 00:42
MHDA- 2024/03/07 00:42
CRDT- 2024/03/06 18:01
PHST- 2023/11/05 00:00 [received]
PHST- 2024/02/15 00:00 [revised]
PHST- 2024/02/23 00:00 [accepted]
PHST- 2024/03/07 00:42 [medline]
PHST- 2024/03/07 00:42 [pubmed]
PHST- 2024/03/06 18:01 [entrez]
AID - S0896-8411(24)00031-3 [pii]
AID - 10.1016/j.jaut.2024.103197 [doi]
PST - aheadofprint
SO  - J Autoimmun. 2024 Mar 5;145:103197. doi: 10.1016/j.jaut.2024.103197.