Analysis of the role of the transcription factor IRF4 for cytotoxic T lymphocyte effector function and memory development

• Applicant: Professorin Dr. Magdalena Huber
• Subject Area: Immunology
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 185202009

• Final Report Year: 2015

Final Report Abstract

The transcription factor (TF) IRF4 belongs to the family of interferon regulatory factors (IRF) consisting of nine members in mice and humans which play important roles in the regulation of innate and adaptive immune responses as well as in oncogenesis. IRF4 has long been known to be essential for the differentiation of the effector CD4+ T cell-subsets Th2, Th9, Th17 and Tfh, however its role for the differentiation of CD8+ T cells has not been closely evaluated until 2013. During the funding period, our group has demonstrated a crucial role of IRF4 for the development of the cytotoxic T lymphocytes (CTL)s and for “low” cytotoxic CD8+ T cell subpopulations including Tc9 and Tc17 cells. Furthermore, we have delineated the supportive function of low cytotoxic Tc9 and Tc17 cells for CD4+ T cell activity in allergic airway disease and autoimmunity of the central nervous system, respectively.

Publications

• IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis. J. Clin. Invest. 2013, 123:247-260
  Huber, Magdalena; Heink, Sylvia; Pagenstecher, Axel; Reinhard, Katharina; Ritter, Josephine; Visekruna, Alexander; Guralnik, Anna; Bollig, Nadine; Jeltsch, Katharina; Heinemann, Christina; Wittmann, Eva; Buch, Thorsten; da Costa, Olivia Prazeres; Brüstle, Anne; Brenner, Dirk; Mak, Tak W.; Mittrücker, Hans-Willi; Tackenberg, Björn; Kamradt, Thomas; ... & Lohoff, Michael
  
• IRF4 provides rations for cytotoxic CD8+ T cell soldiers. Immunity. 2013 39:797-59
  Huber, Magdalena & Lohoff, Michael
  
• Tc9 cells, a new subset of CD8+ T cells, support Th2-mediated airway inflammation. Eur. J. Immunol. 2013. 43:606-618
  Visekruna, Alexander; Ritter, Josephine; Scholz, Tatjana; Campos, Lucia; Guralnik, Anna; Poncette, Lucia; Raifer, Hartmann; Hagner, Stefanie; Garn, Holger; Staudt, Valerie; Bopp, Tobias; Reuter, Sebastian; Taube, Christian; Loser, Karin & Huber, Magdalena
  
• The transcription factor interferon regulatory factor 4 controls peripheral CD8+ T cell differentiation. Proc. Natl. Acad. Sci. USA. 2013. 110:15019-24
  Raczkowski, Friederike; Ritter, Josephine; Heesch, Kira; Schumacher, Valéa; Guralnik, Anna; Höcker, Lena; Raifer, Hartmann; Klein, Matthias; Bopp, Tobias; Harb, Hani; Kesper, Dörthe A.; Pfefferle, Petra I.; Grusdat, Melanie; Lang, Philipp A.; Mittrücker, Hans-Willi & Huber, Magdalena
  
• Heterogeneity in the differentiation and function of CD8+ T cells. Arch. Immunol. Ther. Exp. 2014. 62:449-58
  Mittrücker, Hans-Willi; Visekruna, Alexander & Huber, Magdalena
  
• IRF4 at the crossroad of effector T-cell fate decision. Eur. J. Immunol. 2014. 44:1886-95
  Huber, Magdalena & Lohoff, Michael