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    Research Statement

    Dendritic cells (DCs) are professional antigen-presenting cells (APCs) capable of generating strong T cell dependent primary immune responses. Langerhans cells (LCs) constitute a specialized subset of DCs that reside in their immature state in the epidermis of the skin and pluri-stratified mucosal epithelia, and are capable to present skin-derived antigens to T cells in regional draining lymph nodes upon antigen capture and maturation. The current 'LC paradigm' suggests that LCs act as sentinels in the skin by detecting incoming skin pathogens, integrating the information on both the foreign threat and state of inflammation of the tissue where they originated, and conveying this information to T cells, which subsequently determines both the magnitude and the functional polarization of adaptive immune response to skin antigens. In addition, under "steady-state" non-inflammatory conditions it is thought that LCs play an important role in tolerance.

    Currently Dr Kissenpfennig is a principal investigator within the Centre for Infection and Immunity (CII), and has a long standing in cellualr immunology with particular interest in skin-resident DC populations and their role in adaptive immune responses, and inflammation.  He has recieved funding from the MRC, BBSRC and Wellcome Trust, and has a variety of interactions with the private sector.  His research focuses on the development of novel strategies to deliver vaccines to skin DCs, and on understanding the involvement of key innate cellular (dendritic cells, macrophages) and signalling mechanisms (eg. SOCS) in the promotion of inflammatory diseases, such as allergy, sepsis and cancer. In addition to CII, he also has strong collaborative links with the School of Pharmacy and the Centre for Cancer Research and Cell Biology within the School of Medicine, Dentistry and Biomedical Sciences.

    Previously in the Malissen lab (CIML, France), he developed novel in vivo models that permitted the tracking and conditional ablation of LCs in vivo, and these models have now been widely used within the scientific community to decipher the role of LCs in the skin.  More recently, Dr. Kissenpfennig has linked up with the School of Pharmacy at QUB (Donnelly, Scott and McCarthy Labs) to develop novel strategies to deliver vaccines within the skin utilising nano-particulate formulations and polymeric dissolvable microneedle arrays. Current strategies for antigen delivery within the skin remains an inefficient process, which is limited by the availability of APCs at the site of inoculation. LCs and dermal DCs (dDCs) form a tight semi-contiguous network of APCs in the skin which actively migrate with their antigenic cargo to regional lymph nodes, prime naïve T cells and efficiently initiate robust adaptive immune responses. Recent studies have exemplified that microneedle immunization strategies can induce robust systemic adaptive immune responses following microneedle insertion in the skin. Human and mouse LCs have both been shown to be potent inducers of cytotoxic CD8+ T cells and also induce strong Th1 responses. More recently, the Kissenpfennig lab have found that the activation of IFNγ producing Th1 CD4+ and CD8+ postitive effector T cells responses were predominately mediated by epidermal Langerhans cells following microneedle delivery of nano-encapsulated antigen, and that they were able to both efficiently process and cross-prime antigen-specific CD8+ T cells, therefore validating a novel modality for delivery of vaccines within the skin. This important finding now paves the way to develop novel formulations to improve vaccine compliance, efficacy, stability and safety.

     

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