| The immune system is our primary defense against infection and disease. However, dysregulation of the adaptive immune system can lead to equally threatening autoimmune disease. A key innate immune cell involved in regulating adaptive immune responses is the dendritic cell. We are primarily interested in how the balance between immunity and tolerance is maintained at the barrier surfaces, such as the skin, that faces constant challenge from environmental microorganisms. Two different DC subsets occupy the skin, the epidermal Langerhans cells (LC) and dermal dendritic cells (DDC). Understanding the distinct roles of these DC subsets requires either ablating or restricting the function of each subset. We have shown that a third subset of DC is present within the skin that displays phenotypic and functional characteristics that distinguish it from both LC and DDC. These DC express high levels of the C-type lectin langerin, which is thought to be specific to LC. However, they are radiosensitive and reside in the dermis of the skin, two characteristics common to DDC. In addition, these cells are capable of mediating contact hypersensitivity, an experimental skin immune response similar to the response to poison ivy. These cells are now known as Dermal Langerin+ DC. Interestingly, we also found these cells in the lung and liver, indicating that they are not only important in skin immune responses but may play a role throughout the body. The identification of these cells has uncovered an additional mediator of adaptive immune responses. Additionally, we addressed the role of LC antigen presentation in both the K14-OVAp model of autoimmunity and a similar mouse model that does not develop autoimmunity: K14-mOVA. Our comparisons determined that LC could present both model antigens, but only K14-OVAp resulted in a productive T cell response and autoimmunity. However, using the inducible LC deficient mice and hematopoietic chimeras we discovered that autoimmunity is initiated not by LC or any other DC subset, but by non-hematopoietic cells. It will be important to identify the mechanism of autoimmunity in this model, in order to elucidate an additional mechanism by which adaptive immune responses to skin antigens can be regulated. |
