MEDIZINISCHE KLINIK UND POLIKLINIK I
Gastroenterologie, Hepatologie, Infektiologie, Nephrologie, Endokrinologie, Diabetologie
UNIVERSITÄTSKLINIKUM BONN
Prof. Dr. Christian Strassburg

Wissenschaftliche Studien

Labor für angeborene zelluläre Immunologie - Laboratory for Innate Cellular Immunology

Forschungslabor - Arbeitsgruppe Prof. Dr. Nattermann

Current job advertisement: PhD position

Our group performs translational immunological research studying compartment-specific characteristics of human innate lymphoid cells.

Innate lymphoid cells (ILCs)

ILCs represent a novel family of innate immune cells with lymphoid phenotypes, but lack rearranged antigen receptors. Based on the expression of specific transcription factors, cell-surface markers, and signature cytokines ILCs can be divided into 3 groups.
IFN-g producing, T-bet depending group 1 ILCs (ILC1s) encompass conventional natural killer (cNK) cells as well as CD127(+)ILC1, and the recently characterized CD103(+)ILC1 subset. Group 2 ILCs (ILC2s) are a population of cells that preferentially produce type 2 cytokines, including IL-5 and IL-13, and require GATA3. Group 3 ILCs (ILC3s) can produce IL-17 and/or IL-22, and are dependent on RORyt.

ILCs have been shown to play a significant role in maintaining intestinal health by promoting immunity to pathogens, limiting inappropriate inflammatory responses to commensal bacteria or dietary antigens, or mediating repair following tissue damage.
However, the complexity of intestinal ILC subsets as well as the relation between different ILC subsets is only incompletely
understood. Moreover, due to limited access to human tissues, most of the currently available data regarding ILC phenotype and functions have been obtained in mouse models.

Our aim is to better understand compartment-specific physiological and pathological functions of human innate lymphocytes for immune homeostasis as well as in viral infections and inflammatory diseases.

ILCs and systemic immune activation in HIV infection

Antiretroviral therapy (ART) is highly effective in blocking replication of the human immunodeficiency virus (HIV) and in preventing progression to AIDS. However, there is clear evidence indicating that control of HIV replication does not fully restore human health, with patients on ART still displaying shorter life expectancy due to increased risks for non-AIDS associated morbidities.
Chronic systemic inflammation, characterized by an increased frequency of activated T and B cells, is considered to play an important role in this context. Accordingly, activation of circulating lymphocytes has been shown to be a better predictor for disease progression than HIV plasma load. Of note, markers of immune activation have been shown to be associated with plasma levels of microbial products in HIV infection. Thus, increased levels of circulating microbial products, resulting from microbial translocation, have been proposed to represent a major cause of HIV-induced systemic inflammation. Further studies suggested microbial translocation and systemic inflammation as direct consequences of HIV-associated damage to the gut epithelial barrier.

Recent work of our group indicates HIV-induced alterations of the intestinal ILC pool to be involved in these processes. In current studies we analyse how HIV infection affects compartment-specific composition and function of the intestinal ILC pool and aim at clarifying how these alterations might contribute to systemic immune activation in HIV patients under antiretroviral therapy.

ILCs and liver fibrosis

During the past years we could establish experimental evidence, that human NK cells also display anti-fibrotic activity via induction of hepatic stellate cell (HSC apoptosis). This anti-fibrotic function of cNK cells was linked to the surface expression of distinct molecules such as NKG2D and NKp46 and was importantly modified by factors from the microenvironment, such as neighbouring cells, the local cytokine milieu, and tissue oxygen concentrations.
Recent data obtained in mouse models suggest that ILCs other than cNK cells also modulate hepatic fibrosis. Accordingly, current data of our group indicate that in human inflammatory liver disease both hepatic ILCs, via direct interaction with hepatic stellate cells, as well as intestinal ILCs, via modulating the gut-liver axis, modulate progression of liver fibrosis. Thus, it is the overall aim of the proposed project to analyse how liver disease affects compartment-specific composition and function of the ILC pool and to clarify how these alterations contribute to progression of liver fibrosis.

Members of the lab:

		Jacob Nattermann, MD, Associate Professor Group leader Phone: +49 (0) 228 287 -15966 jacob.nattermann@ukbonn.de
		Dr. Benjamin Krämer PhD, postdoctoral fellow Phone: +49 (0) 228 287 -51415 benjamin.kraemer@ukbonn.de
		Christoph Hoffmeister PhD student Phone: +49 (0) 228 287 -51415 christoph.hoffmeister@ukbonn.de
		Jan Raabe PhD student Phone: +49 (0) 228 287 -51415 jan.raabe@ukbonn.de
		Michael To Vinh PhD student Phone: +49 (0) 228 287 -51415 michael.tovinh@ukbonn.de
		Claudia Finnemann technician Phone: +49 (0) 228 287 -51415 claudia.finnemann@ukbonn.de
		Dominik Kaczmarek MD, postdoctoral fellow Phone: +49 (0) 228 287 -51415 dominik.kaczmarek@ukbonn.de
		Philipp Lutz MD, postdoctoral fellow Phone: +49 (0) 228 287 -51415 philipp.lutz@ukbonn.de
		Felix Goeser postdoctoral fellow Phone: +49 (0) 228 287 -51415 felix.goeser@ukbonn.de

Funding:

Publikationen der Arbeitsgruppe:

Kontakt für Zuweiser:

Tel.: +49 (0) 228 287 -53332
Fax: +49 (0) 228 287 -9019512
e-mail: cm.med1(at)ukbonn.de

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