마우스 피부 이식모델의 갈색 지방에서의 면역반응과 세라마이드대사

Abstract

Abstract Background: Graft rejection is a major drawback of allotransplantation in which T lymphocyte plays a vital role. Lipid metabolism is central to the appropriate differentiation and functions of T lymphocytes while adipose tissues are closely connected with the immune system. However, the characteristics and roles of immune cells are less investigated in the adipose tissues in rejection. Purpose: This study is conducted to elucidate the immune responses in the brown fat in a murine skin graft model. The study could also help understand the role of ceramide metabolism in rejection. Methods: Murine skin graft was performed on the left upper back of recipient mice by using allogeneic mouse tail skin. Mice were sacrificed after 3 or 7 days and immediately frozen in liquid nitrogen and then stored at -80˚C until use for Q-PCR to evaluate the expression of ceramide enzymes. Alternatively, fat tissues were fixed in Formalin for histology. Single cell suspensions were prepared from the brown fats and draining lymph nodes and used for flow cytometry to analyze subsets of T lymphocytes and antigen-presenting cells. Results: I found that there was a significant reduction of brown fat (BF) weight after skin allograft at Day 7, although there were no differences in the numbers of immune cells between syngeneic and allogeneic skin graft mice. The results of flow cytometry show that CD8+ T cells and CD36+ dendritic cells (DCs) were increased by allogeneic skin graft after 7 days, but there was no change in phenotypes of antigen-presenting cells (APCs). The expression of CerS5 and Smpd1 were upregulated in the liver by the allogeneic immune response at Day 7. Conclusion: CD8+ T cells and CD36+ DCs in the BF may contribute to the acute rejection of skin graft. In addition, ceramide metabolism has changed by rejection. Suggesting that fat tissues and lipid metabolisms can be affected by rejection.