Constant rate of steady-state self-antigen trafficking from skin to regional lymph nodes

Abstract

It is suggested that dendritic cells (DCs) capture and present both foreign antigens such as components of pathogens as well as endogenous self-antigens. However, the magnitude of self-antigen trafficking to secondary lymphoid organs is still unclear. Here we show constitutive trafficking of self-antigens from skin to regional lymph nodes (LNs) quantitatively using a KRT14-Kitl transgenic mouse. This mouse model expresses the Kit ligand in keratinocytes, shows hyperpigmentation of the epidermis and exhibits constitutive accumulation of melanin granules (MGs) in skin regional LNs transported by Langerhans cells. Using an MG-solubilization technique, we revealed that 128 μg per week of MGs, a marker of self-antigens, accumulated in skin regional LNs and that the rate of accumulation was constant from 3 to 50 weeks. Activation markers such as CD40, CD54 and CD86 did not increase in the LNs, and abrogation of CD40 signaling did not affect the accumulation. Additionally, the total amount of MGs did not increase significantly following stimulation with intravenous LPS injections. These results suggest that the accumulation is not caused by inflammatory stimuli, and the steady-state trafficking of self-antigens is intrinsically maintained at a constant rate. Because the levels of self-antigens as well as the phenotype of these DCs are thought to be important in the strength of immune responses, the results may imply that the constant rate of trafficking of self-antigens is required for maintaining homeostatic conditions, such as self-tolerance. © 2006 Oxford University Press.