PMID- 37283760
OWN - NLM
STAT- MEDLINE
DCOM- 20230609
LR  - 20230611
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Socs3 expression in myeloid cells modulates the pathogenesis of dextran sulfate 
      sodium (DSS)-induced colitis.
PG  - 1163987
LID - 10.3389/fimmu.2023.1163987 [doi]
LID - 1163987
AB  - INTRODUCTION: Myeloid cells play a critical role in the pathogenesis of 
      Inflammatory Bowel Diseases (IBDs), including Ulcerative Colitis (UC) and Crohn's 
      Disease (CD). Dysregulation of the JAK/STAT pathway is associated with many 
      pathological conditions, including IBD. Suppressors Of Cytokine Signaling (SOCS) 
      are a family of proteins that negatively regulate the JAK/STAT pathway. Our 
      previous studies identified that mice lacking Socs3 in myeloid cells developed a 
      hyper-activated phenotype of macrophages and neutrophils in a pre-clinical model 
      of Multiple Sclerosis. METHODS: To better understand the function of myeloid cell 
      Socs3 in the pathogenesis of colitis, mice with Socs3 deletion in myeloid cells 
      (Socs3 (DeltaLysM)) were utilized in a DSS-induced colitis model. RESULTS: Our 
      results indicate that Socs3 deficiency in myeloid cells leads to more severe 
      colitis induced by DSS, which correlates with increased infiltration of monocytes 
      and neutrophils in the colon and increased numbers of monocytes and neutrophils 
      in the spleen. Furthermore, our results demonstrate that the expression of genes 
      related to the pathogenesis and diagnosis of colitis such as Il1beta, Lcn2, S100a8 
      and S100a9 were specifically enhanced in Socs3-deficient neutrophils localized to 
      the colon and spleen. Conversely, there were no observable differences in gene 
      expression in Ly6C(+) monocytes. Depletion of neutrophils using a neutralizing 
      antibody to Ly6G significantly improved the disease severity of DSS-induced 
      colitis in Socs3-deficient mice. DISCUSSION: Thus, our results suggest that 
      deficiency of Socs3 in myeloid cells exacerbates DSS-induced colitis and that 
      Socs3 prevents overt activation of the immune system in IBD. This study may 
      provide novel therapeutic strategies to IBD patients with hyperactivated 
      neutrophils.
CI  - Copyright (c) 2023 Zhou, Yan, Yang, Buckley, Al Diffalha, Benveniste and Qin.
FAU - Zhou, Lianna
AU  - Zhou L
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, United States.
FAU - Yan, Zhaoqi
AU  - Yan Z
AD  - Gladstone Institute of Neurological Disease, San Francisco, CA, United States.
FAU - Yang, Wei
AU  - Yang W
AD  - Division of Gastroenterology and Hepatology, Weill Cornell College of Medicine, 
      New York, NY, United States.
FAU - Buckley, Jessica A
AU  - Buckley JA
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, United States.
FAU - Al Diffalha, Sameer
AU  - Al Diffalha S
AD  - Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 
      United States.
FAU - Benveniste, Etty N
AU  - Benveniste EN
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, United States.
FAU - Qin, Hongwei
AU  - Qin H
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, United States.
LA  - eng
GR  - R01 NS057563/NS/NINDS NIH HHS/United States
GR  - R01 CA194414/CA/NCI NIH HHS/United States
GR  - P30 AR048311/AR/NIAMS NIH HHS/United States
GR  - P30 AI027767/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230522
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 2.7.10.2 (Janus Kinases)
RN  - 0 (STAT Transcription Factors)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Dextran Sulfate/toxicity
MH  - Janus Kinases/metabolism
MH  - Signal Transduction
MH  - STAT Transcription Factors/metabolism
MH  - *Colitis
MH  - Suppressor of Cytokine Signaling Proteins/genetics
MH  - *Inflammatory Bowel Diseases
MH  - Myeloid Cells/metabolism
MH  - Suppressor of Cytokine Signaling 3 Protein/genetics/metabolism
PMC - PMC10239850
OTO - NOTNLM
OT  - inflammatory bowel diseases (IBDs)
OT  - myeloid cells
OT  - neutrophils
OT  - suppressors of cytokine signaling (SOCS)
OT  - ulcerative colitis (uc)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/06/07 13:10
MHDA- 2023/06/09 06:42
PMCR- 2023/01/01
CRDT- 2023/06/07 09:37
PHST- 2023/02/11 00:00 [received]
PHST- 2023/05/05 00:00 [accepted]
PHST- 2023/06/09 06:42 [medline]
PHST- 2023/06/07 13:10 [pubmed]
PHST- 2023/06/07 09:37 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1163987 [doi]
PST - epublish
SO  - Front Immunol. 2023 May 22;14:1163987. doi: 10.3389/fimmu.2023.1163987. 
      eCollection 2023.