Impaired Mammalian Epimorphic Regeneration in the Absence of Adaptive Immunity

다국어 초록 (Multilingual Abstract)

Regeneration refers to the restoration of damaged tissues or organs to their original structure and function. While mammals exhibit limited regenerative capabilities, digit tip regeneration represents a rare example of epimorphic regeneration, characterized by the formation of a blastema, a mass of undifferentiated cells. This study investigates the role of adaptive immunity in mammalian digit tip regeneration using Rag1-KO mice, which lack functional adaptive immunity. Immunostaining revealed the presence of T cells during digit tip regeneration, suggesting their involvement in the process. In Rag1-KO mice, the absence of adaptive immunity led to reduced nail area and shortened digit tip length. These external changes were accompanied by internal structural deficits, including a reduced mesenchymal area and impaired bone regeneration, characterized by diminished volume and weakness. Single-cell RNA sequencing further demonstrated decreased mesenchymal cell proliferation and late-stage osteogenic differentiation in Rag1-KO mice, confirming that the absence of adaptive immunity influences proliferation and differentiation of blastema. Furthermore, the absence of adaptive immunity resulted in increased infiltration of innate immunity, including macrophages and neutrophils, disrupting the blastema microenvironment. These findings suggest that adaptive immunity indirectly regulates proliferation and differentiation of blastema by modulating innate immunity. This study provides important insights into the role of adaptive immunity in mammalian epimorphic regeneration and offers potential directions for enhancing regenerative outcomes in mammals.

목차 (Table of Contents)

• Abstract Ⅰ
• List of Figures V
• Abbreviations VII
• 1. Introduction 1
• 2. Materials and Methods 7
• 3. Results 12
• 3-1. Adaptive Immunity Is Observed During Digit Tip Regeneration 12
• 3-2. Absence of Adaptive Immunity Reduces Both the Size and Length of
• Regenerated Digit Tips Following Amputation 15
• 3-3. The Regenerated Mesenchymal Area Is Reduced in the Absence of Adaptive
• Immunity 18
• 3-4. Absence of Adaptive Immunity Impairs Bone Regeneration by Reducing
• Volume and Weakening Structure· 20
• 3-5. Proliferation of Mesenchymal Cells Is Reduced in the Absence of Adaptive
• Immunity 25
• 3-6. Osteogenic Cells at Late Differentiation Stages Are Reduced in the Absence
• of Adaptive Immunity 31
• 3-7. The Absence of Adaptive Immunity Disrupts the Regulation of Innate
• Immunity 35
• 4. Discussion 40
• Summary in Korean 45
• References 47
• Acknowledgement 50
• Curriculum Vitae (CV) 53