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Aryl hydrocarbon receptor maintains NOX2-dependent antibacterial immunity in intestinal macrophages

장내 대식세포에서 NOX2 의존적 항균 면역을 유지하는 아릴 탄화수소 수용체에 대한 연구

목차

Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS AND METHODS 5
A. Mice and infection 5
B. BMDM generation 5
C. Cell isolation 6
D. Flow cytometry 7
E. Gene expression 8
F. ELISA 9
G. Immunoblotting 10
H. Statistics 11
Ⅲ. RESULTS 12
A. FICZ stimulation differentially regulates AhR expression in intestinal macrophages of the small intestine and colon. 12
B. BMDM differentiation is independent of AhR. 14
C. AhR does not affect macrophage differentiation in the small intestine and colon 17
D. AhR deficiency in macrophages reduced Il10 production and Foxp3⁺ Tregs in the small intestine, whereas it increased Il10 production and Foxp3⁺ Tregs in the colon 19
E. AhR deficiency differentially regulates Cyp1a1, Il10 and Nox2 expression in colonic macrophages 21
F. AhR deficiency results in cell type-specific downregulation of its downstream signaling components, including Il10, Nox2 and Syk in BMDMs. 23
G. AhR deficiency enhances ATF4 -associated stress response genes in colonic macrophages 25
H. AhR deficiency enhances IL-10 production in response to small intestine metabolites in BMDMs 27
I. AhR-deficient colonic metabolites promote enhanced IL-10 production in BMDMs 29
J. AhR KO mice are more susceptible to C. rodentium infection 31
K. AhR deficiency reduces colonic IL-22 expression during C. rodentium infection 33
L. AhR deficiency increased macrophage phagocytic activity during C. rodentium infection 35
M. AhR deficiency impairs IL-22 production by ILC3 cells during C. rodentium infection 37
N. AhR deficieny does not affect IL-22 production by CD4+ T cells during C. rodentium infection 39
O. AhR deficiency impairs inflammasome and IL-1β production during C. rodentium infection 41
P. AhR deficiency impairs NOX-2 associated gene expression and ROS production during C. rodentium infection 43
Q. Defective inflammasome activation in AhR KO macrophage is regulated by IL-10 and NOX2 induced ROS-dependent pathways 45
IV. DISCUSSION 47
V. CONCLUSION 53
REFERENCES 57
-국문요약- 65

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