Molecular mechanisms of LFA-1 signaling involved in the priming phase of cytotoxic T lymphocytes by different DC subtypes

• Applicant: Dr. Susanne Stutte
• Subject Area: Immunology
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 171071687

• Final Report Year: 2014

Final Report Abstract

Due to technical difficulties we could not follow the anticipated project. I followed some own ideas and could describe plasmacytoid dendritic cells for the first time in visceral adipose tissue of the mouse. We investigated the multistep adhesion cascade required for pDCs to be able to immigrate into visceral adipose tissue and compared it to peripheral LN, liver and spleen. Interestingly, the homing properties are widely shared between adipose tissue and peripheral LN. While P-selectin, integrin α4β1,α4β7 and LFA are necessary; activation of intergrin binding requires Gαi dependent signaling. We could show that CCR7 facilitates immigration. In contrast, S1P signaling mediates the egress from adipose tissue. Chronic inflammation such as extensive HFD as well as aging led to an increase in pDCs in fat tissue. In the future I will follow up the impact of pDC for visceral fat metabolism and the local immune cells.

Publications

• A distinct population of lipid sensing iNKT cells are enriched in fat and protect against diet-induced obesity and insulin resistance. J Immunol 2012 188:176.26
  L. Lynch, R. Tatitori, B. Patrick, S. Stutte, B. Varghese, A. Hogan, S. Balk, D. O’Shea, C. O’Farrelly, U. von Andrian, M. Brenner, M. Excley
  
• Antigen availability is a critical determinant of in vivo CD8+ T cell-dendritic cell interaction kinetics and initiates effector/memory fate decisions. J Immunol 2012 188:110.21
  S. Henrickson, B. Senman, M. Quigley, G. Alexe, S. Stutte, J. Jesneck, M. Iannacone, M. Flynn, S. Imam, I. Mazo, W. Haining, U. von Andrian
  
• Expression and Function of CCL17 in Atopic Dermatitis. Book chapter in "Atopic Dermatitis - Disease Etiology and Clinical Management, InTech February 22, 2012
  S. Stutte, N. Gerbitzki, N. Novak, I. Förster
  
• Intravital two-photon microscopy of immune cells in visceral adipose tissue. J Immunol 2012 188:173.38
  S. Stutte, L. Lynch, U. von Andrian
  
• Antigen availability determines CD8+ T cell-dendritic cell interaction kinetics and memory fate decisions. Immunity. 2013 Sep 19;39(3):496-507
  S. Henrickson, M. Perro, S. Loughhead, B. Senman, S. Stutte, M. Quigley, G. Alexe2, M. Iannacone1, M. Flynn, S. Omid, J. Jesneck, S. Imam, T. Mempel, I. Mazo, W. Haining and U. von Andrian