Staff Profile




General Profile Information
Staff Name Dr Adrien Kissenpfennig
Job Title Senior Lecturer
Location H.S.B Block 10 MBC Site
Room Number 02.020
School School of Medicine, Dentistry and Biomedical Sciences
Contact Details
Telephone +44 (0)28 9097 2295
E-mail a.kissenpfennig@qub.ac.uk
Research Statement
Dendritic cells (DCs) are professional antigen presenting cells 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, which migrate toward cutaneous-draining lymph nodes (CLNs) 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 all of this information to T cells in CLNs, 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. 

My previous research was to establish the exact role of LCs and dermal-derived DCs using genetically engineered mouse models. We recently engineered knock-in mice that express an enhanced green fluorescent protein (EGFP) under the control of the langerin (CD207) gene, a C-Type lectin expressed by LCs which enabled us to further characterize LCs, and directly study the dynamics of LCs both in vivo and ex vivo.  A second knock-in was developed to specifically eliminate LCs in vivo by placing the human diphtheria toxin receptor under the control of the langerin gene.  These transgenic lines will enable us to study the development and function of LCs during both steady-state conditions (tolerance) and in inflammatory contexts.

My research currently focuses on the role of pulmonary DC subsets in different models of lung inflammation.  Recently a major DC population defined to be integrin aE-b7+CD207+CD11b- was found to be specifically localised at the basal lamina of the bronchial epithelia and arterioles of the lung, suggesting that they may be specifically involved in antigen capture and transport to mediastinal lymph nodes of the lung.  Integrin aE-b7+ mediates adhesion of intraepithelial lymphocytes and DCs to E-cadherin, an epithelial specific cadherin involved in cell to cell adhesion.   It is becoming increasingly clear that different DC subsets are involved in specialized roles and effector function. Together these observations suggest that pulmonary CD207+CD11b- DCs are key antigen-presenting cells of the lung capable of migrating across the airway epithelia for antigen sampling, transport and presentation to memory and/or effector cells in regional MLNs. Therefore, the LangEGFP and LangDTR models offer the unique possibility of addressing the role of CD207+ pulmonary DCs both during steady-state and inflammatory conditions, such as viral infection and experimentally induced asthma.  The ability to track and specifically ablate these cells both in vivo and ex vivo may identify these lung DCs as the key proinflammatory cells necessary for Th1 and/or Th2 cell stimulation during airway inflammation.

Furthermore, to align myself with the immunology group within the CII, we are currently investigating the involvement of SOCS proteins in DC cytokine signalling and determining the impact of SOCS protein ablation on DC and T cell development and cell mediated immune responses, and their role in autoimmune disease (in collaboration with Prof Jim Johnston).  I am also investigated the role of ARF6 (GTP binding protein) in T cell activation and anergy through the use of in vitro models and the development of an ARF6 conditional knockout model.

As part of the DEL All-Ireland Research Base grant I am also collaborating with key members of the CII to establish key in vivo models of respiratory and infectious disease.  Four Home Office project licences have been written and are awaiting ethical approval to commence work with these models.

 

 





Professional Qualifications

External PhD examiner for University of Glasgow (February 2013)

External PhD examiner for Trinity College Dublin (March 2013)





Membership Of Other Societies / Professional Activities

Since my appointment at QUB I have undertaken several external research activities, which reflect my expertise in my research domain, which are, summarised below: 

 

 

Invited Research Presentations

 

  • MUGEN EU Network of Excellence, Athens (April 2006)
  • BSI Immunology group, Edinburgh University (June 2006)
  • DC-THERA EU Network of Excellence, Holland (June 2006) 
  • National Institute of Immunology, India (November 2006)
  • Nikolas Symposia on Langerhans Cell Histiocytoses, Athens (June 2007)
  • The British Society of Oral Maxillofacial Pathology, Belfast (May 2008)
  • Roslin Institute, Edinburgh (September 2010)
  • Joint Meeting of the ISI/UIG Annual Conference, Belfast (September 2010)
  • Royal Society of Microscopy, Belfast (July 2010)
  • University of Otago, New Zealand (September 2011)
  • University of Lancaster (May 2012)
  • Keynote BSI Northern England Immunology Annual Symposium (June 2012)
  • Centre d’Immunologie Seminar, France (August 2012)
  • EMBO Meeting, Dr Jekyll and Mr Hyde: The Macrophage in Inflammation and Immunity, France (January 2013)
  • Glasgow University, Keynote for The Burn Retreat (February 2013)
  • University of Cork, Ireland (March 2013)
  • Joint Meeting of the ISI/UIG Annual Conference, Belfast (September 2013)
  • 13th International Langerhans Cell Workshop, Netherlands (October 2013)
  • Cardiff University (March 2014)

 

 

Key Established International Collaborations with Leading Researchers

 

  • Prof Padraic Fallon (Trinity College Dublin) – DEL ‘All-Island’ Research
  • Prof Bernard Malissen (CIML, France)
  • Dr Uwe Ritter (University of Regensburg, Germany)
  • Dr Peter Hammerl (University of Salzburg, Austria)
  • Dr Florent Ginhoux (A*STAR Immunology Institute, Singapore)
  • Dr Rachael Rigby (University of Lancaster, UK) - MRC
  • Dr Anne Moore (University of Cork, Ireland) - HRB
  • Dr Muzlifah Haniffa (Newcastle University, UK) - BSF 

 

External Peer Reviewer

 

Scientific Journals

 

  • Journal of Investigative Dermatology
  • Trends in Immunology
  • Vaccine
  • Blood
  • Immunology
  • Journal of Pharmacy and Pharmacology

 

Funding Bodies

 

  • Health Research Board (IRE)
  • MRC Research Grant (UK)
  • Wellcome Trust Clinical Fellowships (UK)
  • ANR Research Grants (F)

 

 

Consultancy

 

  • Consultant for Innate Pharma Biotech, France (Jan 2007 – Jun 2008)
  • Expert Panel for Sanofi Pasteur MSD, France (April 2008)

 

 

Member of the Ulster Immunology Group Steering Committee (2007 - present)

 

  • Currently Treasurer since 2009

 





Publications
Journal(s)
TitleJournal NameYear
Langerin(+) Dermal Dendritic Cells Are Critical for CD8(+) T Cell Activation and IgH gamma-1 Class Switching in Response to Gene Gun Vaccines Journal of Immunology Vol 186 (1377-1383)  DOI   2011
Cell-to-Cell Interactions and Signals Involved in the Reconstitution of Peripheral CD8(+) T-CM and T-EM Cell Pools PLoS ONE Vol 6 (1377-1383)  DOI   2011
Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration Development Vol 138 (3647-3656)  DOI   2011
Integrated T-cell receptor and costimulatory signals determine TGF-β-dependent differentiation and maintenance of Foxp3+ regulatory T cells. European Journal of Immunology Vol 41(5) (1242-1248)  DOI 2011
The Role of Direct Presentation by Donor Dendritic Cells in Rejection of Minor Histocompatibility Antigen-Mismatched Skin and Hematopoietic Cell Grafts Transplantation Vol 91 (154-160)  DOI   2011
Development of atopic dermatitis-like inflammation is critically dependent on Langerhans cells in mice. Clinical & Experimental Dermatology Vol 19 (183-183)  2010
Langerhans Cells Prime IL-17-Producing T Cells and Dampen Genital Cytotoxic Responses following Mucosal Immunization Journal of Immunology Vol 184 (4842-4851)    2010
Vasodilator-Stimulated Phosphoprotein Regulates Inside-Out Signaling of beta(2) Integrins in Neutrophils Journal of Immunology Vol 184 (6575-6584)  DOI   2010
CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells. The Journal of experimental medicine Vol 207(1) (189-206)  DOI   2010
Foxp3+ T cells induce perforin-dependent dendritic cell death in tumor-draining lymph nodes. Immunity Vol 32(2) (266-278)  DOI   2010
Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope. Journal of Immunology Vol 183(1) (430-437)  DOI 2009
Loss of the LAT adaptor converts antigen-responsive T cells into pathogenic effectors that function independently of the T cell receptor. Immunity Vol 31(2) (197-208)  DOI   2009
Peripheral Thy1+ lymphocytes rearranging TCR-gammadelta genes in LAT-deficient mice. European Journal of Immunology Vol 39(9) (2596-2605)  DOI 2009
Alloantigen-specific de novo-induced Foxp3+ Treg revert in vivo and do not protect from experimental GVHD. European Journal of Immunology Vol 39(11) (3091-3096)  DOI 2009
Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. The Journal of experimental medicine Vol 206(13) (3089-3100)  DOI   2009
Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice Journal of Cellular and Molecular Medicine Vol 13 (2658-2672)  DOI   2009
Priming of CD8(+) and CD4(+) T Cells in Experimental Leishmaniasis Is Initiated by Different Dendritic Cell Subtypes Journal of Immunology Vol 182(2) (774-783)    2009
Antigen-specific T-T interactions regulate CD4 T-cell expansion Blood Vol 112(4) (1249-1258)  2008
Insights into Langerhans Cell Function from LC Deficient Mice European Journal of Immunology Vol 38(9) (2369-2376)    2008
Retrovirus-specificity of regulatory T cells is neither present nor required in preventing retrovirus-induced bone marrow immune pathology. Immunity Vol 29(5) (782-794)  DOI 2008
Cutting edge: Langerin+ dendritic cells in the mesenteric lymph node set the stage for skin and gut immune system cross-talk. Journal of Immunology Vol 180(7) (4361-4365)    2008
Langerin expressing cells promote skin immune responses under defined conditions. Journal of Immunology Vol 180(7) (4722-4727)    2008
ZAP-70 restoration in mice by in vivo thymic electroporation. PLoS ONE Vol 3(4) (e2059-e2059)  DOI   2008
Antigen specific T-T interactions regulate CD4 T cell expansion. Blood Vol Prepublished (0-0)  DOI   2008
Tumor immunotherapy by epicutaneous immunization requires langerhans cells. Journal of Immunology Vol 180(3) (1991-1998)    2008
Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells. Journal of Immunology Vol 180(3) (1565-1575)    2008
The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells. The Journal of experimental medicine Vol 204(13) (3119-3131)  DOI   2007
Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state. The Journal of experimental medicine Vol 204(13) (3133-3146)  DOI   2007
Identification of a novel population of Langerin+ dendritic cells. The Journal of experimental medicine Vol 204(13) (3147-3156)  DOI   2007
Epidermal Langerhans Cells are Dispensable for Humoral and Cell-Mediated Immunity Elicited by Gene Gun Immunization. Journal of Immunology Vol 179(2) (886-893)    2007
Mature DC from skin and skin-draining LN retain the ability to acquire and efficiently present targeted antigen. European Journal of Immunology Vol 37(5) (1184-1193)  DOI   2007
Langerhans cells--revisiting the paradigm using genetically engineered mice. Trends in Immunology Vol 27(3) (132-139)  DOI   2006
Visualization of the earliest steps of gammadelta T cell development in the adult thymus. Nature Immunology Vol 7(9) (995-1003)  DOI   2006
Disruption of the langerin/CD207 Gene Abolishes Birbeck Granules without a Marked Loss of Langerhans Cell Function Molecular and Cellular Biology Vol 25(1) (88-99)  DOI   2005
Dynamics and Function of Langerhans Cells In Vivo: Dermal Dendritic Cells Colonize Lymph Node Areas Distinct from Slower Migrating Langerhans Cells Immunity Vol 22(5) (643-654)  DOI   2005
Cloning and characterization of the mouse homologue of the human dendritic cell maturation marker CD208/DC-LAMP European Journal of Immunology Vol 33(9) (2619-2629)    2003
Identification of mouse langerin/CD207 in Langerhans cells and some dendritic cells of lymphoid tissues Journal of Immunology Vol 168(2) (782-792)    2002
The mouse and human IGSF6 (DORA) genes map to the inflammatory bowel disease 1 locus and are embedded in an intron of a gene of unknown function. Immunogenetics Vol 52(1-2) (112-120)    2000
Conference Contribution(s)
TitleYear
SOCS are Essential for Macrophage Polarisation with Consequential Effects on Tumour Outcome 2011
The role of suppressor of cytokine signalling (SOCS)-2 in B cell development and function 2010
The role of SOCS2 and SOCS3 in macrophage plasticity and inflammation 2010
Function of lung langerin-positive dendritic cells in a model of respiratory viral infection 2010
Impact of SOCS2 on plasmacytoid DC biology and interferon response 2010
Function of lung langerin-positive dendritic cells in a model of respiratory viral infection 2009