Abstract
Why and when the immune system skews to Th2 mediated allergic immune responses is still poorly characterized. With two homologous lipocalins, the major respiratory dog allergen Can f 1 and the human endogenous, non-allergenic Lipocalin-1, we investigated their impact on human monocyte-derived dendritic cells (DC). The two lipocalins had differential effects on DC according to their allergenic potential. Compared to Lipocalin-1, Can f 1 persistently induced lower levels of the Th1 skewing maturation marker expression, tryptophan breakdown and interleukin (IL)-12 production in DC. As a consequence, T cells stimulated by DC treated with Can f 1 produced more of the Th2 signature cytokine IL-13 and lower levels of the Th1 signature cytokine interferon-γ than T cells stimulated by Lipocalin-1 treated DC. These data were partially verified by a second pair of homologous lipocalins, the cat allergen Fel d 4 and its putative human homologue major urinary protein. Our data indicate that the crosstalk of DC with lipocalins alone has the potential to direct the type of immune response to these particular antigens. A global gene expression analysis further supported these results and indicated significant differences in intracellular trafficking, sorting and antigen presentation pathways when comparing Can f 1 and Lipocalin-1 stimulated DC. With this study we contribute to a better understanding of the induction phase of a Th2 immune response.
Highlights
Dendritic cells (DC) act at the interface of innate and adaptive immunity orchestrating signals from both to induce the most suitable immune response to a given antigen
Moderated statistics based on Uptake and cellular targeting of lipocalins in human monocyte-derived DCs
Data suggest the influence of individual susceptibility to allergens and the circumstances at the time-point of T-cell activation as well as the crosstalk between DCs and allergens to be critical for the decision to drive a specific T-helper cell subtype [30,31,32]
Summary
Dendritic cells (DC) act at the interface of innate and adaptive immunity orchestrating signals from both to induce the most suitable immune response to a given antigen. Interleukin-10 and TGF-b are the cytokines necessary for the differentiation of regulatory T cells which upon differentiation express IL-10 and TGF-b [2,3,4]. This differentiation of the T cell populations, directed by the crosstalk of the antigen with the antigen presenting DCs and several signals from the innate immune system is the main bias towards the kind of the developing immune response [1]
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