Mouse Lung CD103⁺ and CD11b^high Dendritic Cells Preferentially Induce Distinct CD4⁺ T-Cell Responses

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.

Bronchial Epithelial Cells Induce Alternatively Activated Dendritic Cells Dependent on Glucocorticoid Receptor Signaling

“…This observation fits to the proposed function of CD11b + pulmonary DCs to be less migratory (30,31) and mediate Th2 cell immunity (32)(33)(34). The data suggest that ECCM DCs adopt a phenotype that resembles a phenotype of alternative activation in macrophages and therefore represent alternatively activated or tolerogenic DCs.…”

GM-CSF–Licensed CD11b+ Lung Dendritic Cells Orchestrate Th2 Immunity to Blomia tropicalis

“…As the IRF8 mutation is not restricted solely to the DC compartment in the BXH2 model, this may have complicated their findings. In contrast, data from another group showed that CD11b + DCs isolated from steady state lungs preferentially primed Th2 responses, whereas CD103 + DCs promoted Th1 and Th17 polarization (28). Another study using intratracheal adoptive transfer suggested that only CD11b + DCs were able to initiate allergic sensitization to D. pteronyssinus (27).…”

“…However, due to conflicting reports (27)(28)(29), which subset of lung-resident DCs is responsible for the induction of Th2 priming remains a subject of debate.…”

“…However, these cells mainly act at the late stage of inflammation by secreting chemokine and presenting Ag within the lung tissue (27). The exact contribution of each lung-resident DC subset to the pathogenesis of dust mite allergy is not conclusive, as studies using ex vivo sorted lung DCs have led to conflicting reports about the contribution of CD103 + and CD11b + DCs to Th2 priming (27)(28)(29). In addition, although mouse models that permit the selective depletion of lung CD103 + DCs exist (30,31), it has only recently been possible to specifically deplete resident lung CD11b + DCs.…”

Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity

“…20 presenting cells to the lung mucosa, when compared to other recombinant poxvirus vectors (Trivedi et al, 2014), by eventually conferring a different T-cell functionality (Furuhashi et al, 2012). Similarly, canarypox recombinants can elicit qualitatively distinct cytokine and chemokine profiles compared to attenuated VV vectors in rhesus macaques (Teigler et al, 2014).…”