CERIC Center of Excellence for Research on Inflammation and Cardiovascular disease

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Professor in Medical Microbial Pathogenesis, Department of Medical Biochemistry and Biophysics, Chemistry I, Karolinska Institutet

Phone +46 8 524 877 81

Group members

Nylén, Frank, PhD-student
Rekha, Rokeya Sultana, PhD-student
Miraglia, Erica, forsknings ingenjör
Lindh, Monica BMA, forskningslaborant

Birgitta Agerberth

My group is working on antimicrobial peptides (AMPs) or host defense peptides, which are effector molecules in innate immunity, constituting the front line of our defense system against invading pathogens at epithelial barrier. Our main focus is to study the mechanism and regulation during induced expression of AMPs and to identify potent inducers in order to strengthen the epithelial barrier against invading pathogens. These inducers are potential drug-targets against infections. Due to induction of multiple AMPs with different mechanisms of action the risk of developing bacterial resistance can be considered low. This is an important advantage of utilizing induced endogenous defense molecules to fight infections. AMPs are also included in the microbicidal armament of phagocytes and secreted from neutrophils. In health AMPs help eliminate pathogens and maintain homeostasis with the normal flora. In addition to the microbicidal activity, AMPs have been demonstrated to function as chemo‐attractants for cells of both the adaptive and innate immunity and are able to modulate immune responses. Thus, AMPs constitute a link between the innate and adaptive immunity.

When CERIC started 2008, there were some reports on both pro-inflammatory and anti-inflammatory activities of AMPs. This was a line of research we wanted to follow-up within CERIC. We have mainly studied the human cathelicidin LL-37 that we originally discovered and we see this peptide as a marker for the complete AMP system in humans. Recent advances in our understanding of the function of AMPs have associated their dys-regulated production with various autoimmune or auto-inflammatory diseases such as psoriasis, arthritis, or systemic lupus erythematosus. It has been demonstrated that LL-37 forms complexes with self DNA that is recognized by plasmacytoid dendritic cells (pDC) via TLR 9, triggering the release of type-I interferon that drives the inflammation. In collaboration we have now demonstrated a similar mechanism in the development of type 1 diabetes in NOD (non-obese-diabetic) mice.
Within CERIC we have studied the interaction between LL-37 and eicosanoids in several cell-types. We have detected the expression of LL-37 in synovial biopsies and identified the peptide in synovial fluid of rheumatoid arthritis (RA) patients. In pristane-induced arthritis (PIA), an animal model of arthritis that closely mimics RA, the rat cathelicidin (rCRAMP) is strongly up-regulated in the joints of arthritic animals.

Research interactions with CERIC

  • Crosstalk between LL-37 and eicosanoids
  • The involvement of cathelicidins (rCRAMP and LL-37) in arthritis
  • The involvement of cathelicidins (rCRAMP and mCRAMP) in the development of diabetes