SEMA4A Contributes Eosinopillic Phenotypes in Asthma and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Yohei Maeda, Masaki Hayama, Kazuya Takeda, Atsushi Kumanogoh, Hidenori Inohara

We previously reported that the class IV semaphorin SEMA4A was critical for Th1/Th2 regulation and that eosinophilic airway inflammation was enhanced in SEMA4A-deficient mice. However, the role of SEMA4A in eosinophils and human eosinophilic airway inflammation is still unknown.


We compared serum SEMA4A levels in patients with asthma and CRSwNP vs healthy individuals by enzyme-linked immunosorbent assay (ELISA), and examined SEMA4A expression in nasal polyps by immunohistochemistry. We cultured bone marrow cells from Wild Type mice (WT mice) and SEMA4A-deficient mice with recombinant IL-5, and evaluated the recovery of the bone marrow-derived eosinophils (BMDEos). In addition, we determined the number of eosinophils in the spleen from WT mice or SEMA4A-deficient mice.


Levels of SEMA4A were significantly elevated in sera from patients with asthma and CRSwNP than healthy individuals. (mean±SEM 3588±840 and 2403±618 versus 445±214). We found that SEMA4A was strongly expressed in eosinophils in the nasal polyps by immunohistochemistry. BMDEos and the number of splenic eosinophils from SEMA4A-deficient mice were significantly lower than those from WT mice (mean±SEM 2.14±0.23×107 versus 1.41±0.10×107, 5973±189/106 versus 4100±750/106, respectively).


Our results suggested that SEMA4A had trophic functions for eosinophils in human and mice. SEMA4A may promote eosinophil survival and disease activity in patients with asthma and CRSwNP.