PMID- 25978359
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 5
DP  - 2015
TI  - The Involvement of Immune Semaphorins in the Pathogenesis of Inflammatory Bowel 
      Diseases (IBDs).
PG  - e0125860
LID - 10.1371/journal.pone.0125860 [doi]
LID - e0125860
AB  - BACKGROUND AND AIMS: Immune semaphorins are a large family of proteins involved 
      in the pathogenesis of inflammatory diseases through the regulation of immune 
      homeostasis and tissue inflammation. We aim to assess the possible involvement of 
      semaphorin3A (sema3A) and 4A (sema4A) in peripheral immune responses and bowel 
      tissue inflammation of patients suffering from Crohn's disease (CD) and 
      ulcerative colitis (UC). PATIENTS AND METHODS: Twenty-seven CD patients and 10 UC 
      patients were studied and compared to 10 patients followed for acute 
      diverticulitis (disease control) and 12 healthy individuals. All were evaluated 
      for sema3A expression on T regulatory cells (Tregs), serum levels of sema3A and 
      sema4A, and tissue expression of sema3A and sema4A in bowel biopsies. RESULTS: 
      The percentage (%) of T regulatory cells (Tregs) expressing sema3A in patients 
      with active CD (64.5% +/- 14.49%) and active UC (49.8% +/- 16.45%) was significantly 
      lower when compared to that of healthy controls (88.7% +/- 3.6%, p< 0.001 and p< 
      0.0001, respectively). This expression was seen to be in negative correlation 
      with CD activity. Serum levels of Sema4A were significantly lower in patients 
      with CD and UC when compared to that of controls (5.69 +/- 1 .48 ng\ml for CD, 5.26 
      +/- 1.23 ng/ml for UC patients vs 9.74 +/- 2.73 ng/ml for normal controls, P<0.001). 
      Sema4A was highly expressed in lymphocytes of the lamina propria of CD and UC 
      patients but absent in patients with diverticulitis or in normal individuals. 
      CONCLUSIONS: Altered % of Tregs expressing sema3A in patients with inflammatory 
      bowel diseases (IBD) is partially responsible for their failure in preventing 
      CD4+ effector T cell induced inflammation in IBD in peripheral blood. The 
      increased expression of sema4A in bowel biopsies from CD and UC patients is 
      suggestive of its central role in regulating local tissue inflammation in the 
      bowel.
FAU - Vadasz, Zahava
AU  - Vadasz Z
AD  - Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion, 
      Haifa, Israel.
FAU - Rainis, Tova
AU  - Rainis T
AD  - Division of Gastroenterology, Bnai Zion Medical Center, Technion, Haifa, Israel.
FAU - Nakhleh, Afif
AU  - Nakhleh A
AD  - Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion, 
      Haifa, Israel.
FAU - Haj, Tharwat
AU  - Haj T
AD  - Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion, 
      Haifa, Israel.
FAU - Bejar, Jacob
AU  - Bejar J
AD  - Department of Pathology, Bnai Zion Medical Center, Technion, Haifa, Israel.
FAU - Halasz, Katty
AU  - Halasz K
AD  - Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion, 
      Haifa, Israel.
FAU - Toubi, Elias
AU  - Toubi E
AD  - Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion, 
      Haifa, Israel.
LA  - eng
PT  - Journal Article
DEP - 20150515
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (SEMA3A protein, human)
RN  - 0 (SEMA4A protein, human)
RN  - 0 (Semaphorin-3A)
RN  - 0 (Semaphorins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Case-Control Studies
MH  - Colitis, Ulcerative/immunology/metabolism/*pathology
MH  - Crohn Disease/immunology/metabolism/*pathology
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Semaphorin-3A/*analysis/blood
MH  - Semaphorins/*analysis/blood
MH  - T-Lymphocytes, Regulatory/immunology/metabolism
MH  - Young Adult
PMC - PMC4433250
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/05/16 06:00
MHDA- 2016/02/18 06:00
PMCR- 2015/05/15
CRDT- 2015/05/16 06:00
PHST- 2014/11/04 00:00 [received]
PHST- 2015/03/24 00:00 [accepted]
PHST- 2015/05/16 06:00 [entrez]
PHST- 2015/05/16 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
PHST- 2015/05/15 00:00 [pmc-release]
AID - PONE-D-14-48656 [pii]
AID - 10.1371/journal.pone.0125860 [doi]
PST - epublish
SO  - PLoS One. 2015 May 15;10(5):e0125860. doi: 10.1371/journal.pone.0125860. 
      eCollection 2015.