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It could be deemed appropriate to view terrestrial vertebrates as a combination of many species and their genetic build as a composite of genes embedded in their own genome and in the genomes of affiliated microbial partners: the microbiome.
The body’s large surfaces, harbouring many resident commensals, are, however, also exposed to potentially harmful micro-organisms. These surfaces include the skin and the gastro-intestinal tract.
Several barriers are in place to prevent microbes invading our bodies, the first of which is the epithelial cell layer. Although sufficient to prevent invasion by most microbes, this is not always adequate.
A second line of defence is formed by cells of the immune system, providing protection against those microbes that overcome the epithelial barrier or which invade the body after trauma.
Interestingly, many commensal micro-organisms are highly beneficial to us and are instrumental in mediating physiologically important chemical transformations, whilst the cells of the epithelial barrier themselves are important for nutrient processing and uptake. Hence, an immune reaction at these sites needs to be tightly controlled and tailored to the potential threat-level of the micro-organisms detected (commensals vs. harmful opportunistic pathogens), with minimal damage to self, and with swift resolution and wound repair.
Our laboratory studies the role that cells of the immune system play at the initiation, modulation and resolution of immune responses at epithelial barrier sites. These studies provide insights into the mechanisms that control the maintenance of a resident population of micro-organisms, promoting healthy living, and the prevention of undesirable immune responses that may result in chronic infections, allergies, autoimmunity and an increased risk of cancer.
Veldhoen M, Brucklacher-Waldert V. (2012) Dietary influences on intestinal immunity.
Nat Rev Immunol. 12 (10):696-708
Ferreira C, Veldhoen M (2012) Host and microbes date exclusively.
Cell 149 1428-1430
Mastelic B, Freitas do Rosario AP, Veldhoen M, Renauld J C, Jarra W, Sponaas A-M, Roetynck S, Stockinger B, Langhorne J (2012) IL-22 protects against liver pathology and lethality of an experimental blood-stage malaria infection.
Frontiers in Inflammation 3:85
Veldhoen M Direct interactions between intestinal immune cells and the diet.
Moens E, Veldhoen M (2012) Epithelial barrier biology: good fences make good neighbours.
Immunology 135 1-8
Li Y, Innocentin S, Withers DR, Roberts NA, Gallagher AR, Grigorieva EF, Wilhelm C, Veldhoen M (2011) Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation."
Cell 147 629-640
Press release relating to this publication
More information about the publication and Marc Veldhoen
Media coverage relating to this publication
Report on the BBSRC website
Article in BBSRC 'Business' publication (pg10-11)
Zygmunt BM, Veldhoen M (2011) T helper cell differentiation: more than cytokines.
Advances in Immunology 209 159-196
Stockinger B, Hirota K, Duarte J, Veldhoen M (2011) External influences on the immune system via activation of the aryl hydrocarbon receptor.
Seminars in Immunology 23, 99-105
Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, Ahlfors H, Wilhelm C, Tolaini M, Menzel U, Garefalaki A, Potocnik AJ, Stockinger B (2011) Fate mapping of IL-17-producing T cells in inflammatory responses.
Nature Immunology 12, 255-263
Teixeira-Coelho M, Cruz A, Carmona J, Sousa C, Ramos-Pereira D, Saraiva AL, Veldhoen M, Pedrosa J, Castro AG, Saraiva M (2011) TLR2 deficiency by compromising p19 (IL-23) expression limits Th 17 cell responses to Mycobacterium tuberculosis.
International Immunology 23 89-96
Veldhoen M, Withers DR (2010)
Innate lymphoid cell relations.
Science 330 594-595
Veldhoen M, Duarte JH (2010) The aryl hydrocarbon receptor: fine-tuning the immune-response.
Current Opinion in Immunology 22 747-752
Veldhoen M (2010)
A toxin-sensitive receptor able to reduce immunopathology.
Nature Immunology 11 779-781
Veldhoen M (2010)
Interferon regulatory factor 4: combinatorial control of lymphocyte differentiation.
Immunity 33 141-143
Veldhoen M, Seddon B (2010)
Empowering T helper 17 cells in autoimmunity.
Nature Medicine 16 166-168
Hirota K, Martin B, Veldhoen M
(2010) Development, regulation and functional capacities of Th17 cells.
Seminars in Immunopathology 32 3-16
Veldhoen M, Stockinger B (2010)
Response: Characteristics of IL-17-producing γδ T cells.
Immunity 32 2
Martin B, Hirota K, Cua DJ, Stockinger B, Veldhoen M (2009)
Interleukin-17-producing γδ T cells selectively expand in response to pathogen products and environmental signals.
Immunity 31 321-330
Saraiva M, Christensen JR, Veldhoen M, Murphy TL, Murphy KM, O'Garra A (2009)
Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose.
Immunity 31 209-219
Veldhoen M (2009)
The role of T helper subsets in autoimmunity and allergy.
Current Opinion in Immunology 21 606-611
Bending D, De La Pena H, Veldhoen M, Phillips JM, Uyttenhove C, Stockinger B, Cooke A (2009)
Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice.
Journal of Clinical Investigation 119 565-572
Stockinger B, Veldhoen M, Hirota K (2009)
Modulation of Th17 development and function by activation of the aryl hydrocarbon receptor - the role of endogenous ligands.
European Journal of Immunology 39 652-654
Veldhoen M, Hirota K, Christensen J, O'Garra A, Stockinger B (2009)
Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells.
Journal of Experimental Medicine 206 43-49
Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, Buer J, Martin B, Wilhelm C, Stockinger B (2008)
Transforming growth factor-β 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset.
Nature Immunology 9 1341-1346
Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld J-C, Stockinger B
(2008) The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins.
Nature 453 106-109
O'Garra A, Stockinger B, Veldhoen M (2008)
Differentiation of human TH-17 cells does require TGF-β!.
Nature Immunology 9 588-590
Stockinger, B., Veldhoen, M. (2007)
Differentiation and function of Th17 T cells.
Current Opinion in Immunology 19 281-286
Stockinger B, Veldhoen M, Martin B (2007)
Th17 T cells: linking innate and adaptive immunity. Seminars in Immunology 19 353-361
Veldhoen M (2007)
Oral tolerance - passing CD11b on the way to tolerance.
Immunology and Cell Biology 85 397-398
Veldhoen, M., Stockinger, B. (2006)
TGFβ1, a 'Jack of all trades': the link with pro-inflammatory IL-17-producing T cells.
Trends in Immunology 27 358-361
Veldhoen M, Hocking RJ, Flavell RA, Stockinger B (2006)
Signals mediated by transforming growth factor-β initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease.
Nature Immunology 7 1151-1156
Veldhoen M, Moncrieffe H, Hocking RJ, Atkins CJ, Stockinger B (2006)
Modulation of dendritic cell function by naive and regulatory CD4+ T cells.
Journal of Immunology 176 6202-6210
Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B (2006)
TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells.
Immunity 24 179-189
Comment on ScienceWatch website:
Barthlott T, Moncrieffe H, Veldhoen M, Atkins CJ, Christensen J, O'Garra A, Stockinger B (2005)
CD25+CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production.
International Immunology 17 279-288
Veldhoen M, Magee AI, Penha-Goncalves MN, Stockinger B (2005)
Transduction of naive CD4 T cells with kinase-deficient Lck-HIV-Tat fusion protein dampens T cell activation and provokes a switch to regulatory function.
European Journal of Immunology 35 207-216
Cristina Ferreira (senior Post-doc)
Beata Zygmunt (Post-doc)
Emmanuelle Moens (Post-doc, Visiting Scientist)
Silvia Innocentin (Research Assistant)
Jörg Stange (Post-doc)
Spela Konjar (Post-doc)
Verena Brucklacher-Waldert (Post-doc/visiting worker)
Yunhua Loo (PhD-student)
Anne-Katrien Stark (Post-doc in collaboration with Klaus Okkenhaug and Cellzome)
Marc Veldhoen studied Medical Biology at the Faculty of Medicine, Utrecht University, and continued his career in the Stockinger-lab at the National Institute for Medical Research (Mill Hill) where he obtained his PhD in 2003. During his post-doctoral work at the NIMR he was the first to describe the de novo differentiation of the new Th17 and Th9 subsets of T helper cells. He went on to show the importance of Th17 cells in the initiation of autoimmune responses, their plasticity, and, via the identification of the Aryl Hydrocarbon Receptor in Th17 and IL-17 producing TCRγδ cells, established a link between the environment and auto-immunity. In 2010 he moved to the Babraham Institute to take up a position as group leader. He continued his work on the AhR and discovered a direct link between dietary phytochemicals and the maintenance of epithelial immune cells. He was awarded a prestigious 2010 ERC Staring Independent Research grant, and selected into the esteemed EMBO young investigator programme in 2011.
Babraham Institute - Babraham Research Campus - Cambridge - United Kingdom