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Precision-cut Mouse Lung Slices to Visualize Live Pulmonary Dendritic Cells
Published on: April 5, 2017
Mouse lung CD103+ and CD11bhigh dendritic cells preferentially induce distinct CD4+ T-cell responses
Kazuki Furuhashi1, Takafumi Suda, Hirotsugu Hasegawa
1Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. suda@hama-med.ac.jp
Insights
Mouse lung dendritic cells (LDCs) have two subtypes: CD103(+) LDCs and CD11b(high) LDCs. CD103(+) LDCs induce T helper 1 (Th1) and Th17 responses, while CD11b(high) LDCs promote Th2 responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Mouse lung dendritic cells (LDCs) comprise two main subpopulations: CD103(+) CD11b(low/negative) LDCs and CD103(-) CD11b(high) LDCs.
- While functional differences exist, their distinct roles in T helper (Th) cell response induction remain unclear.
Purpose of the Study:
- To investigate whether CD103(+) and CD11b(high) LDCs preferentially induce different Th cell responses.
- To elucidate the specific Th cell polarization capabilities of these LDC subsets.
Main Methods:
- Naive DO11.10 CD4(+) T cells were co-cultured with either CD103(+) or CD11b(high) LDCs from BALB/c mice.
- Primed CD4(+) T cells were restimulated to assess cytokine secretion, intracellular cytokine expression, and chemokine receptor mRNA levels.
Main Results:
- CD4(+) T cells primed by CD103(+) LDCs produced significantly higher levels of IFN-γ and IL-17A (Th1/Th17).
- CD4(+) T cells primed by CD11b(high) LDCs secreted significantly higher levels of IL-4, IL-6, and IL-10 (Th2).
- Differential expression of chemokine receptors (CXCR3/CCR5 for Th1; CXCR4/CCR4 for Th2) correlated with LDC priming.
Conclusions:
- Mouse CD103(+) LDCs predominantly induce Th1 and Th17 immune responses.
- Mouse CD11b(high) LDCs primarily drive Th2 immune responses under steady-state conditions.
- These findings highlight distinct functional roles for LDC subsets in shaping adaptive immunity.
Abstract:
Mouse lung dendritic cells (LDCs) have been recently shown to contain two major subpopulations: CD103(+) CD11b(low or negative) (CD103(+) LDCs) and CD103(-) CD11b(high) LDCs (CD11b(high) LDCs). Although several studies have demonstrated functional differences between them, it is unclear whether the subpopulations induce distinct T helper (Th) cell responses. The present study was conducted to examine whether CD103(+) and CD11b(high) LDCs preferentially generate different Th responses. Naive DO11.10 CD4(+) T cells were primed with CD103(+) or CD11b(high) LDCs obtained from normal BALB/c mice. The primed CD4(+) T cells were restimulated, and their cytokine secretions were assessed. The expression of intracellular cytokines and the mRNA levels of chemokine receptors were also measured. We found that the CD4(+) T cells primed with CD103(+) LDCs secreted significantly larger amounts of IFN-γ and IL-17A, whereas those primed with CD11b(high) LDCs released significantly higher levels of IL-4, IL-6, and IL-10. Intracellular cytokine assay showed that CD103(+) LDCs induced greater frequencies of CD4(+) T cells producing IFN-γ and IL-17A, whereas CD11b(high) LDCs were more efficient at inducing CD4(+) T cells producing IL-4 and IL-10. The mRNA levels of CXCR3 and CCR5, which are expressed preferentially in Th1 cells, were significantly higher in CD4(+) T cells primed with CD103(+) LDCs. The mRNA levels of CXCR4 and CCR4, which are expressed primarily in Th2 cells, were significantly greater in those primed with CD11b(high) LDCs. These data suggest that mouse CD103(+) LDCs predominantly elicit Th1 and Th17 responses, whereas CD11b(high) LDCs primarily provoke a Th2 response under the steady state.
