Reina Mebius

Functional development of the immune system 

The generation of an immune response is dependent on efficient interaction of rare antigen-specific T cells with dendritic cells that present the antigen. Lymph nodes are organized to mediate an efficient interaction of antigen presenting cells and T cells. Thus, lymph nodes are viewed as professional immune response factories. Within inflammatory lesions that are characteristic of autoimmune disease, a organized lymphoid structure, named tertiary lymphoid structures, are found. It is likely that in the case of autoimmune diseases, a high degree of organization will worsen the disease since efficient presentation of autoantigens will enhance activation of autoreactive T cells. However, these structures have also been reported to develop in response to a persistent pathogen, and in this case they may in fact facilitate the process of pathogen elimination.
We are delineating the cellular and molecular mechanisms that mediate the differentiation of stromal cells towards lymphoid tissue organizing cells, allowing the attraction of hematopoietic cells to the developing lymph nodes. In addition, the subsequent differentiation of these cells into the different stromal cell subsets that are present within lymph nodes are studied. Furthermore, similar processes are examined during the development of tertiary lymphoid structures in chronic inflammatory diseases.
In addition, we have shown that  stromal are able to act as antigen presenting cells themselves. We are addressing the role of stromal cells as antigen presenting cells, as well as their influence on the antigen presenting function of dendritic cells.

Prof. dr. Reina Mebius is chair of the NVVI - the Dutch Society for Immunology.

Key publications

Randall TD, Mebius RE. The development and function of mucosal lymphoid tissues: a balancing act with micro-organisms. Mucosal Immunol. 7:455-66, 2014.

van de Pavert SA, Ferreira M, Domingues RG, Ribeiro H, Molenaar R, Moreira-Santos L, Almeida FF, Ibiza S, Barbosa I, Goverse G, Labão-Almeida C, Godinho-Silva C, Konijn T, Schooneman D, O'Toole T, Mizee MR, Habani Y, Haak E, Santori FR, Littman DR, Schulte-Merker S, Dzierzak E, Simas JP, Mebius RE, Veiga-Fernandes H. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity. Nature. 508:123-7, 2014

Koning J.J., Gijs Kooij, Helga E De Vries, Martijn Nolte, Reina Mebius. Mesenchymal stem cells are mobilized from the bone marrow during inflammation, Frontiers in Antigen Presenting Cell Biology, 2013, Front. Immunol., 04 March 2013 | http://dx.doi.org/10.3389/fimmu.2013.00049.

Baptista AP, Olivier BJ, Goverse G, Greuter M, Knippenberg M, Kusser K, Domingues RG, Veiga-Fernandes H, Luster AD, Lugering A, Randall TD, Cupedo T, Mebius RE. 2012. Colonic patch and colonic SILT development are independent and differentially regulated events. Mucosal Immunol. 2012 Sep 19. doi: 10.1038/mi.2012.90. 

van de Pavert, S.A., Olivier, B.J., Goverse, G., Vondenhoff, M.F., Greuter, M., Beke, P., Kusser, K., Höpken, U.E., Lipp, M., Niederreither, K., Blomhoff, R., Sitnik, K., Agace, W.W., Randall, T.D., de Jonge, W.J., Mebius, R.E. CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat Immunol , 10:1193-1199, 2009.

Overview of publications of Reina Mebius Group: http://www.ncbi.nlm.nih.gov/pubmed/?term=mebius+r

Contact details: Email r.mebius@vumc.nl; Phone 020-4448076