S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Ph.D. / Sc.D._의학과)
CCL7, CCR3 and IL-17 in a murine model of allergic rhinitis
알레르기비염 마우스모델에서 CCL7 및 CCR3와 IL-17의 관계
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의학과 면역학 전공, 2013. 2. 이재서.
- Background: The proinflammatory cytokine IL-17, produced by Th17 cells, plays a critical role in neutrophilic airway inflammation. Recent reports suggest that IL-17 is associated with eosinophil infiltration into nasal mucosa in a murine model of allergic rhinitis. The chemokine receptor CCR3, which is found on the surface of eosinophils, is involved in allergic diseases such as asthma, atopic dermatitis and allergic rhinitis. CCL7, a ligand of CCR3, induces chemotaxis of monocytes, eosinophils, basophils, NK cells and T lymphocytes.
Objectives: In this study we investigated whether IL-17 deficiency suppresses allergic inflammation in a murine allergic rhinitis model. We also determined the relationship between IL-17 and the CCL7/CCR3 pathway of eosinophil infiltration.
Methods: IL-17A-deficient and wild-type (WT) BALB/c mice were sensitized and challenged with ovalbumin to induce allergic rhinitis. Parameters of allergic responses including the nasal symptom score, serum immunoglobulin levels, and eosinophil infiltration and cytokine production in nasal mucosa were analyzed. The mRNA and protein levels of CCL7 and CCR3 in nasal tissue and serum in the two groups were compared. The chemotactic response to CCL7 in bone marrow-derived eosinophils (bmEos) from WT and IL-17 knockout (KO) mice was measured in the presence or absence of anti-IL-17 antibody.
Results: In the allergic rhinitis model, IL-17 deficiency can significantly decrease nasal symptoms, OVA-specific IgE in serum, and eosinophil infiltration and cytokine production in the nasal mucosa. The CCL7 concentration in nasal lavage fluid and serum of IL-17 KO mice was lower than that in the control group. Compared to WT mice, CCL7 mRNA level was suppressed and CCR3 mRNA and protein levels were decreased in the nasal mucosa of IL-17 KO mice. In the absence of IL-17 stimulation during differentiation, the bmEos from WT mice showed a decreased chemotactic response to CCL7. The bmEos from IL-17 KO mice showed a significantly decreased chemotactic response to 500 ng/ml CCL7. In addition, among leukocytes only eosinophils showed decreased CCR3 expression in IL-17 KO-OVA mice.
Conclusions: Suppression of nasal inflammation by IL-17 deficiency in allergic rhinitis is partly responsible for the regulation of CCL7 secretion and eosinophil infiltration, which may be regulated by the CCL7/CCR3 pathway.