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Batf3 selectively determines acquisition of CD8+ dendritic cell phenotype and function
Janin Chandra1, Paula T Y Kuo1, Anne M Hahn1
1The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Queensland, Australia.
Immunology and Cell Biology
|November 30, 2016
Summary
Transcription factor Batf3 is not essential for CD8+ dendritic cell (DC) development. In Batf3-deficient mice, CD8+ DCs adopt a CD11b+ DC fate, impacting immune responses.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Batf3 (basic leucine zipper transcription factor, ATF-binding partner 3) influences CD103+ tissue-resident dendritic cell (DC) development.
- The role of Batf3 in CD8+ DC development is debated, with Id2 (inhibitor of differentiation 2) being essential for CD8+ DC development.
Purpose of the Study:
- To investigate the necessity of Batf3 for CD8+ DC development and function.
- To clarify the role of CD8+ DCs in immune responses like skin graft rejection.
- To understand DC subtype commitment and plasticity.
Main Methods:
- Utilized bone marrow chimeric mice with targeted deletion of Id2 in the CD11c compartment.
- Analyzed Batf3 knockout (Batf3-/-) mice.
- Assessed skin graft rejection and delayed hypersensitivity responses.
- Characterized CD8+ DC populations using flow cytometry for markers like CD11b, CD4, CD172α, IRF4, and IRF8.
- Evaluated antigen uptake, cleavage, and phagocytosis capabilities of DCs.
Main Results:
- Mice lacking Id2 in CD11c+ cells showed impaired skin graft rejection and delayed hypersensitivity.
- Batf3-/- mice maintained competence in skin graft rejection and delayed hypersensitivity.
- Batf3-/- mice possessed CD8+ DCs expressing CD11b, CD4, CD172α, and IRF4, but lacked IRF8.
- CD8+ DCs in Batf3-/- mice could process antigens but failed to phagocytose dying cells.
- Absence of Batf3 led to CD8+ DCs adopting characteristics of CD11b+ DCs.
Conclusions:
- CD8+ lineage DCs are crucial for initiating immune responses against neo-antigens in skin graft rejection.
- Batf3 is not absolutely required for CD8+ DC development.
- In the absence of Batf3, CD8+ DCs exhibit plasticity, potentially differentiating into CD11b+ DCs.
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