Abstract
Abstract Systemic autoimmune diseases such as lupus are characterized by inflammation in many organs. The role of local tissue-resident immune cells in specific organ involvement in these diseases remains unclear. We evaluated the role of Langerhans cells (LC) as prototypic tissue-resident dendritic cells (DC) in eliciting local immune defects in the MRL model of lupus. Injection of diphtheria toxin (DT) in Lang-eGFP.DTR knock-in mice results in depletion of langerin+ dermal DC (dDC) and LC. To assess LC’s role in systemic autoimmunity, we introgressed the knock-in mutation from the stock B6 onto the MRL background. Serial DT injections every 7-10 days exacerbate inflammation in the skin (King et al) and cornea in MRL but not in B6 mice. To investigate underlying mechanisms, we assessed the effect of LC depletion on T cells in skin/eye draining cervical lymph nodes (cLN). There was a significantly higher proliferation of CD8+, but not CD4+, T cells in cLN of LC-ablated than control mice; such effect was not seen in spleen CD8+ T cells. Also, LC-ablated MRL, but not B6 mice, exhibited reduced CD62L on cLN T cells. Further, freshly isolated dDC were more efficient than LC in promoting the proliferation of CD8+, but not CD4+, cNL T cells. Such local regulation of CD8+ T cells may play a role in immune tolerance locally. A defect in this mechanism owing to reduced LC migration in MRL mice (Eriksson and Singh, 2008) may confer skin/eye inflammation, without affecting other organs
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