Breaking the Triad: Immune Tolerance Induction Without Antigen Co-Presentation via Tim Agonist for the Treatment of Autoimmune Diseases
Abstract
1. Introduction
2. Results
2.1. Optimization of DilC18(5) Dye Incorporation in Liposomes
2.2. Liposomal Formulations and Lymphatic Uptake
2.2.1. Relative Fluorescence Intensity by Lipid Type
2.2.2. Fluorescent Immunohistochemistry and Free DilC18(5) Uptake
2.2.3. Liposome Uptake and Immune Cell Colocalization by Formulation
2.2.4. Quantitative Colocalization Analysis
B Cell Colocalization
T Cell Colocalization
2.3. Pharmacology of LPX3 Liposomes
2.3.1. In Vitro Pharmacology
2.3.2. In Vivo Pharmacology
2.4. Effect of LPX3 Liposomes in MOG35–55 Experimental Autoimmune Encephalomyelitis (EAE) Model
2.4.1. Prophylactic Effects of LPX3 and LPX3/MOG35–55 in the EAE Model
2.4.2. Therapeutic Effects of LPX3 in the EAE Model
Disease Progression and Clinical Scores
Overall Survival in Treated vs. Untreated Mice
2.4.3. Ex Vivo Analysis of CD4+Foxp3+ T Cells in Treated vs. Untreated Mice
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Animal Housing and Handling
4.3. DilC18(5) Dye Screening
4.4. Liposomal Formulation Preparation for Colocalization Studies
4.5. Liposomal Formulation for MOG-EAE Studies
4.6. Lymphatic Uptake Quantification
4.6.1. Fluorescence Imaging
4.6.2. Colocalization Analysis
4.7. In Vivo Pharmacology
4.8. EAE Study
4.8.1. Group Assignment
Prophylactic
Therapeutic
Survival Analysis
4.8.2. Ex Vivo Splenocyte Isolation and Flow Cytometry Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
DMPC | 1,2-dimyristoyl-sn-glycero-3-phophocholine |
DOPC | 1,2-dioleoyl-sn-glycero-3-phophocholine |
DSPC | 1,2-distearoyl-sn-glycero-3-phophocholine |
POPC | 1-palmitoyl-2oleoyl-sn-glycer-3-phosphocholine |
MOG | Myelin oligodendrocyte glycoprotein |
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Karzoun, B.; Ramadan, A.; Allababidi, S.; Fathallah, A.M. Breaking the Triad: Immune Tolerance Induction Without Antigen Co-Presentation via Tim Agonist for the Treatment of Autoimmune Diseases. Int. J. Mol. Sci. 2025, 26, 5531. https://doi.org/10.3390/ijms26125531
Karzoun B, Ramadan A, Allababidi S, Fathallah AM. Breaking the Triad: Immune Tolerance Induction Without Antigen Co-Presentation via Tim Agonist for the Treatment of Autoimmune Diseases. International Journal of Molecular Sciences. 2025; 26(12):5531. https://doi.org/10.3390/ijms26125531
Chicago/Turabian StyleKarzoun, Basel, Abdulraouf Ramadan, Saleh Allababidi, and Anas M. Fathallah. 2025. "Breaking the Triad: Immune Tolerance Induction Without Antigen Co-Presentation via Tim Agonist for the Treatment of Autoimmune Diseases" International Journal of Molecular Sciences 26, no. 12: 5531. https://doi.org/10.3390/ijms26125531
APA StyleKarzoun, B., Ramadan, A., Allababidi, S., & Fathallah, A. M. (2025). Breaking the Triad: Immune Tolerance Induction Without Antigen Co-Presentation via Tim Agonist for the Treatment of Autoimmune Diseases. International Journal of Molecular Sciences, 26(12), 5531. https://doi.org/10.3390/ijms26125531