The Involvement of Immune Semaphorins in the Pathogenesis of Inflammatory Bowel Diseases (IBDs)

Abstract

Background and AimsImmune 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 MethodsTwenty-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.ResultsThe 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±1.48ng\ml for CD, 5.26±1.23 ng/ml for UC patients vs 9.74±2.73ng/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.ConclusionsAltered % 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.

Decreased Expression of Semaphorin3A/Neuropilin-1 Signaling Axis in Apical Periodontitis

“…Many proinflammatory cytokines expressed in periapical sites are responsible for stimulating bone resorption accompanied by periapical inflammation. A recent study revealed that Sema3A expression was downregulated in rheumatoid arthritis [ 15 ] and inflammatory bowel disease [ 26 ], which was in accordance with our results. Meanwhile, studies showed that Sema3A binding to Nrp1 alleviated inflammation and the progression of autoimmune arthritis by reducing anticollagen IgG levels and suppressing the release of IFN- γ and IL-17 [ 16 ], which are considered to be critical in mediating inflammation in diseases [ 14 ].…”

Aggravated mucosal and immune damage in a mouse model of ulcerative colitis with stress

“…The incidence of UC has recently increased (3). The pathogenesis of UC is associated with various factors, including genetic predisposition (4), environmental risk factors (5) and the state of the immune system (6). Furthermore, the disorder of the immune system is considered an important factor (7), and psychological stress is considered one of the risk factors for UC (8).…”

Semaphorin‐3E attenuates intestinal inflammation through the regulation of the communication between splenic CD11C+ and CD4+CD25− T‐cells

“…These findings, along with the observation of an increase of CD11c, CD86 markers in the absence of SEMA3E, suggest that Sema3E has an important role in regulating potential DC activation and the associated T‐cell response during colonic inflammation. A previous study already highlighted a role for SEMA3E in the regulation of a particular T‐cell population in IBD (Vadasz et al, ), but nothing is known about SEMA3E in this context. However, this proves the importance of the SEMA family in T‐cell response, and further exploratory works will be undertaken to confirm our hypothesis with SEMA3E.…”