Inducible ablation of Langerhans cells enhances skin immune responses (48.15)

Abstract

Abstract Although initially thought to be required for the development of contact hypersensitivity (CHS) responses, recent data obtained from two Langerhans cell (LC)-deficient mouse models has cast this role in doubt. We have previously described huLangerin-DTA mice in which LC are constitutively ablated but other Langerin+ DC are unaffected. In these mice, the absence of LC leads to the development of increased CHS responses. In the second model, muLangerin-DTR mice, LC and Langerin+ dermal dendritic cells (dDC) are inducibly ablated by administration of DT. LC, unlike Langerin+ dDC, repopulate slowly after diphtheria toxin (DT) administration. By comparing early and late time-points after DT administration, it appears that Langerin+ dDC are required for optimal CHS responses and efficient epicutaneous immunization but that LC are redundant. One major difference between these two models that could account for the disparate results is the timing of LC ablation: inducible (muLangerin-DTR) vs. constitutive (huLangerin-DTA). We now report the development of a new line of mice (huLangerin-DTR) in which administration of DT leads to inducible ablation of LC without affecting Langerin+ dDC. The acute and selective ablation of LC in these mice results in increased CHS responses. Thus, LC-mediated suppression does not require their absence during ontogeny or during the steady state. Rather, LC actively limit cutaneous immune responses and may function to terminate ongoing cutaneous immune responses and/or prevent responses against epidermal antigens.