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Research Programmes

Molecular Medicine

Macrophage biology: regulation of gene expression

Antonio Celada

Antonio Celada

Group Leader
Professor of Immunology (Physiology Dept. - UB)
Office Tel : +34 93 40 37165
Lab Tel : +34 93 403 71 64
e-mail : antonio.celadairbbarcelona.org

Background

Macrophages are produced in the bone marrow and are located in all the organs of the body, where they differentiate and become microglia (brain), Kupffer cells (liver), Langerhans cells (skin), dendritic cells, among others. Macrophages are critical in the immune system as they directly phagocytize and destroy bacteria, fungi, parasites and virus. They also release a large number of molecules that regulate the function of other cells. For example, they produce TNF-α or IL-1, which are responsible for the production of fever. They also present the antigens processed as peptides to T lymphocytes, an obligatory step to produce immunological memory, the basis for vaccine activity. Macrophages not only destroy micro-organisms but also play a key role in wound healing, tissue repair and vascularization. Finally, these cells have important functions outside of the immune system, such as the control of iron or lipid metabolisms. The dendritic cells that derive from macrophages are potent antigen-presenting cells and at the present are used in clinical trials to induce immunity against tumors or to remove the HIV virus from infected patients under treatment.

Research Interests

Our research involves the use of genomics and proteomics tools to study the molecular mechanisms involved in macrophage proliferation, activation, differentiation and entry in apoptosis following stimulation with cytokines or growth factors. We aim to determine the signal transduction pathways for macrophages and to establish how the various genes involved in the functional activity of these cells are regulated. Given that the major histocompatibility complex class II genes are critical for antigen presentation to T lymphocytes, we address the regulation of the expression of these genes. We also study gene dysregulation in macrophage immunosenescence.

Research Lines

Regulation of genes that determine the proliferation, differentiation, activation and apoptosis of macrophages.
We study the first steps of signal transduction that either determine macrophage proliferation or activation. A particular focus is on the regulation of MAP kinases and the corresponding phosphatases. We also examine the processes of classical and alternative activation of macrophages and in particular the role of arginase. For classical activation, we address the regulation of MHC class II genes.

Aging and dysregulation of gene expresion in the immune system.
We have found that aged mice lack a protein that mediates signalling for proliferation, differentiation and protection from apoptosis. We aim to identify the mechanisms that inhibit the expression of this protein and to determine the role of telomers in macrophage aging and also that of several proteins involved in DNA repair.

Funding

This group receives financial supprot from the following sources:

  • Ministerio de Educación y Ciencia (Spanish Ministry of Science and Education)
  • European Commission (FP6 and FP7)
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Institute for Research in Biomedicine (IRB Barcelona)
Parc Científic de Barcelona
C/ Baldiri Reixac 10
08028 Barcelona - Spain
Tel: +34 93 402 02 50 | Fax: +34 93 403 71 14
infoarrobairbbarcelona.org