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Cellular-FLIP, Raji isoform (c-FLIP R) modulates cell death induction upon T-cell activation and infection

Tanja Telieps1, Frida Ewald, Marcus Gereke

  • 1Laboratory of Systems-Oriented Immunology and Inflammation Research, Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, Magdeburg, Germany.

European Journal of Immunology
|March 19, 2013
PubMed

Insights

Cellular-FLIP-related inhibitor of protein R (c-FLIPR) is induced in lymphocytes and protects against apoptosis. c-FLIPR expression in immune cells enhances the response to bacterial infections, reducing tissue damage.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Death Regulation

Background:

  • Dysregulated apoptosis, stemming from imbalanced pro- and anti-apoptotic proteins, contributes to diseases like cancer and autoimmune disorders.
  • Cellular-FLIP (c-FLIP) proteins, including isoforms c-FLIPL and c-FLIPS, regulate apoptosis at death receptors but the role of c-FLIPR is unclear.
  • Understanding c-FLIPR is crucial for its potential role in immune responses and disease pathogenesis.

Purpose of the Study:

  • To investigate the function of the poorly understood c-FLIPR isoform in vivo.
  • To determine the role of c-FLIPR in lymphocytes and its impact on immune responses.
  • To analyze the effects of c-FLIPR expression on apoptosis and bacterial infection outcomes.

Main Methods:

  • Demonstrated induction of endogenous murine c-FLIPR in activated lymphocytes.
  • Generated transgenic mice with specific hematopoietic cell expression of murine c-FLIPR.
  • Assessed lymphocyte apoptosis in vitro and immune response to Listeria monocytogenes infection in vivo.

Main Results:

  • Lymphocytes from c-FLIPR transgenic mice exhibited protection against CD95-induced apoptosis in vitro.
  • Transgenic mice showed normal cell counts and immune cell subset frequencies in steady state.
  • c-FLIPR transgenic mice displayed reduced liver necrosis and improved bacterial clearance following Listeria monocytogenes infection.

Conclusions:

  • Endogenous c-FLIPR is induced in activated lymphocytes.
  • Hematopoietic c-FLIPR expression protects against apoptosis and enhances immune response to bacterial infections.
  • c-FLIPR plays a significant role in supporting an effective immune defense against pathogens.

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