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흰쥐 가슴샘 재생과정에서 IL-17A의 발현 특성

Expression of IL-17A during Thymus Regeneration in the Rat

박종훈|김봉선|백선용|이희우|오세옥|윤식|최학종
대한체질인류학회|2011.09|해부·생물인류학 (Anatomy & Biological Anthropology)|제24권 제3호|pp. 141-154|DOI 10.11637/aba.2011.24.3.141

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ThymusIL-17가슴샘상피세포가슴샘IL-17A가슴샘버팀질세포가슴샘세포가슴샘 재생Thymic stromal cellsThymocytesThymic epithelial cellsThymus regeneration
주제분류해부학

초록

IL-17A는 활성화된 T 세포에 의해 분비되는 사이토카인으로 5개의 연관된 사이토카인인 IL-17B, IL-17C, IL-17D, IL-17E 및 IL-17F과 함께 IL-17 family로 분류되며, 이들은 모두 유사한 단백질 구조를 가지고 있다. IL-17A와 IL-17F는 활성화된 T 세포에서 발현되는 반면 IL-17B, IL-17C, IL-17D 및 IL-17E는 모든 조직에서 광범위하게 발현되며 이들의 기능은 IL-17A와 부분적으로 일치하지만 이에 관해서 자세히 연구되어 있지않다. 가슴샘버팀질세포는 가슴샘세포의 증식, 성숙 및 분화의 조절에 중요한 역할을 하는 것으로 알려져 있기 때문에, 본 연구에서는 가슴샘세포, 가슴샘상피세포, 큰포식세포, 가슴샘가지돌기세포 및 가슴샘종양세포에서 역전사 중합효소 연쇄반응법을 이용하여 IL-17 family의 발현 특성을 확인하였다. 또한 cyclophosphamide를 흰쥐에투여하여 가슴샘의 급성 퇴축을 유발시킨 다음 3, 7 및 14일째 실험 동물을 희생시켜, 가슴샘 재생과정 동안 시간의 경과에 따른 IL-17 family와 IL-17 수용체(IL-17R)의 발현특성을 역전사 중합효소 연쇄반응법을 통해 조사하였으며, IL-17A의 경우는 면역조직화학법을 이용하여 그 발현양상을 더 구체적으로 분석하였다. 그 결과IL-17A와 IL-17E는 가슴샘종양세포에서만 발현되었고 IL-17C는 큰포식세포를 제외한 모든 세포에서 발현되고있음을 확인하였다. IL-17F의 경우 실험군의 모든 세포에서 발현된 반면에 IL-17B와 IL-17D는 전혀 발현되지않았다. 또한 IL-17A는 가슴샘 재생과정 중 가슴샘세포와 가슴샘버팀질세포에서 모두 증가되었으며 IL-17A의수용체인 IL-17R은 재생모델의 가슴샘세포와 가슴샘버팀질세포에서 발현양이 거의 유사하였다. 면역조직화학법을 이용한 분석에서도 재생과정 동안 상피세포에서 IL-17A의 발현이 증가됨을 확인하였다. 따라서 가슴샘세포와 가슴샘 상피세포에서 IL-17A의 발현 및 그 수용체를 통한 신호전달은 가슴샘의 급성퇴축 이후 가슴샘이 재생되는 과정에 중요한 역할을 할 것으로 생각된다.

Abstract

IL-17A is a pro-inflammatroy cytokine secreted by activated T cells. The IL-17 family consist of IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. IL-17A and IL-17F are produced primarily in activated T cells. In contrast, IL-17B, IL-17C, IL-17D and IL-17E are expressed in a wide assortment of tissues. Their functions partially overlap those of IL-17A, although they have not been as thoroughly investigated. The receptor for IL-17A (IL-17R) is widely expressed in a variety of tissues. IL-17A and IL-17E mRNAs were expressed in only EL4 cells. IL-17C mRNA expression was observed in the thymic subcapsular/cortex epithelial cells (SNEC), cortex or cortical reticular cells (CREC), medullary epithelial cells (MEC), medullary interdigitating-like cells (MDC), thymocytes and EL4 cells. However, IL-17C mRNA was not expressed in RAW 264.7 cells. Immunohistochemical study also demonstrated not only the presence of IL-17A mainly in the thymic epithelial cells, but also the upregulated expression of IL-17A in the thymic epithelial cells of the regenerating thymus. Thus, the results of the present study suggest that IL-17A expressed in the thymocytes and thymic epithelial cells could play an important role in the development of new T cells to replace T cells damaged by cyclophosphamide treatment during thymus regeneration.

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