title: The Involvement of Immune Semaphorins in the Pathogenesis of Inflammatory Bowel Diseases (IBDs).
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion, Haifa, Israel.
authors.forename: Zahava
authors.initials: Z
authors.lastname: Vadasz
authors.affiliation: Division of Gastroenterology, Bnai Zion Medical Center, Technion, Haifa, Israel.
authors.forename: Tova
authors.initials: T
authors.lastname: Rainis
authors.affiliation: Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion, Haifa, Israel.
authors.forename: Afif
authors.initials: A
authors.lastname: Nakhleh
authors.affiliation: Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion, Haifa, Israel.
authors.forename: Tharwat
authors.initials: T
authors.lastname: Haj
authors.affiliation: Department of Pathology, Bnai Zion Medical Center, Technion, Haifa, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Bejar
authors.affiliation: Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion, Haifa, Israel.
authors.forename: Katty
authors.initials: K
authors.lastname: Halasz
authors.affiliation: Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion, Haifa, Israel.
authors.forename: Elias
authors.initials: E
authors.lastname: Toubi
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D040121:Semaphorin-3A / Q000032:analysis* / Q000097:blood; D039961:Semaphorins / Q000032:analysis* / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: C108639:SEMA3A protein, human; C574096:SEMA4A protein, human; D040121:Semaphorin-3A; D039961:Semaphorins