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장 조직 내 대식세포의 새로운 항원흡수기전을 통한 장 면역조절

Gut Immune Regulation by Intenstinal CX3CR1+ Phagocytes via unique antigen uptake pathway

초록/요약

Various immune cells in mucosal tissues protect the host body from infection and are essential for homeostasis. This study is investigated how macrophages that express CX3CR1 play an important role for intestinal immune regulation. Gut macrophage expressing CX3CR1 has been reported to uptake circulatory antigens from blood vessels. CX3CR1+ macrophage in the gut lead to the generation of CD8+ T cells through cross-presentation. CD8+ T cell primed by CX3CR1+ macrophage through antigen uptake, and it express various cytokines to protect intestinal immunity. Intestinal CX3CR1+ macrophages can induce B cells to produce IgA with IL-9 and IL-13 secreted by CD8+ T cells activated through cross-presentation. Macrophages have a variety of receptors involved in antigen uptake. Among them, it noted for the mannose receptor (CD206) of macrophages. The mannose receptor, commonly called CD206, is expressed on the macrophage surface. Because there were reported of cross-presentation with the antigen uptake through CD206, the experiment was applied using CD206 knock-out mouse. The object of the study is to investigate whether circulatory antigen uptake by intestinal CX3CR1+ macrophages is CD206 dependent pathway. However, CD206 independent antigen uptake was found in the intestine of CX3CR1+ macrophage. In addition, CD8+ T cell priming and IgA production were also independent on CD206. When extracellular vesicle inhibitor was treated, circulatory antigen uptake of gut macrophages was significantly decreased. Taken together, these results suggested that intestinal CX3CR1+ macrophages could utilize unique antigen uptake machinery independently through CD206.

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목차

I. INTRODUCTION 1
II. MATERIALS AND METHODS 3
A. Mice 3
B. Antigen uptake of macrophage 3
C. Immunization and cell depletion 3
D. Cell isolation 3
E. T cell proliferation 4
F. Flow cytometry 5
G. Enzyme-Linked ImmunoSorbent Assay (ELISA) 5
H. Statistics 6
III. RESULTS 7
A. CD206 expression on intestinal mucosa CX3CR1+ macrophages 7
B. CD206 is dispensable for circulatory antigen uptake of gut macrophages 9
C. Antigen uptake of CX3CR1+ macrophages in vitro 12
D. Deficiency of CD206 leads to decreased cross-presentation activity of intestinal mucosa CX3CR1+ macrophages to prime CD8+ T cells in vitro 14
E. Deficiency of CD206 is not critical for cross-presentation activity of intestinal mucosa CX3CR1+ macrophages to prime CD8+ T cells in vivo 16
F. CD206 is unnecessary for mucosal IgA production from B cells 18
G. Antigen uptake of intestinal mucosa CD206 CX3CR1+ macrophages through Extracellular vesicles 20
IV. DISCUSSION 22
V. CONCLUSION 24
REFERENCES 25
KOREAN ABSTRACT 27

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