During my PhD-studies (Prof. M. Kapsenberg; AMC, Univ. of Amsterdam), I studied the flexibility of allergen-specific Th2 cells and the role of microbial priming of human dendritic cells for the development of regulatory T cells. During a subsequent post-doc period in the lab of Prof. B. Lambrecht (currently at Ghent University, Ghent, Belgium) the role of microbial-primed dendritic cells in protection against allergic airway inflammation was studied in different mouse models. Under auspices of a ZonMW-VENI grant (2006-2009) I continued in the lab of Prof M. Yazdanbakhsh (LUMC, Leiden) and investigated the causal relationship between chronic helminth infection and protection against allergic airway disease, focusing on the role of different helminth-induced regulatory cells in protection against allergic airway disease. This work formed the basis for current research line in which the role of helminth-induced regulatory B and T cells and dendritic cell modulation in protection against allergic diseases form important components.
My main interest involves host immune regulation induced by worm parasites and other microbes that are part of our microbiome, and how they can protect against inflammatory diseases, such as allergy and asthma. The research is conducted both mouse models and in humans. The ultimate goal is to identify parasite-derived molecules and regulatory mechanisms that can be used for novel therapies of lung diseases such as allergic asthma. This work is currently supported by a VIDI grant from ZonMW and a Lung Foundation consortium grant.
Smits HH, van der Vlugt LE, von Mutius E, Hiemstra PS. 2016. Childhood allergies and asthma: New insights on environmental exposures and local immunity at the lung barrier. Curr Opin Immunol. 42:41-47.
Smits HH, Hiemstra PS, Prazeres da Costa C, Ege M, Edwards M, Garn H, Howarth PH, Jartti T, de Jong EC, Maizels RM, Marsland BJ, McSorley HJ, Müller A, Pfefferle PI, Savelkoul H, Schwarze J, Unger WW, von Mutius E, Yazdanbakhsh M, Taube C. 2016. Microbes and asthma: Opportunities for intervention. J Allergy Clin Immunol.;137(3):690-7.
Schmiedel Y, Mombo-Ngoma G, Labuda LA, Janse JJ, de Gier B, Adegnika AA, Issifou S, Kremsner PG, Smits HH, Yazdanbakhsh M. 2015. CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel. PLoS Negl Trop Dis.;9(8):e0003995
van der Vlugt LE, Haeberlein S, de Graaf W, Martha TE, Smits HH. 2014. Toll-like receptor ligation for the induction of regulatory B cells. Methods Mol Biol. 1190:127
van der Vlugt LEM, Adegnika AA, Zinsou FJ,Ozir-Fazalalikhan A, Kremsner PG, Yazdanbakhsh M, Smits HH. 2014. IL-10 producing CD1dhi B cells from Schistosoma haematobium-infected individuals induce IL-10 producing T cells and suppress effector T cell cytokines. J Inf Dis 210:1207
van der Vlugt LEMP, Mlejnek E, Ozir-Fazalalikhan A, Dijksman TR, Labuda LA, Schot R, Hiemstra PS, Möller GM, Yazdanbakhsh M, Smits HH. 2014. Less IL-10 producing CD24hiCD27+ B cells in response to LPS in allergic asthma patients. Clin Exp Allergy 44:517.
Wammes LJ, Hamid F, Wiria AE, Wibowo H, Sartono E, Maizels RM, Smits HH, Supali T, Yazdanbakhsh M. 2012. Regulatory T cells in human lymphatic filariasis: stronger functional activity in microfilaremics. PLoS Negl Trop Dis, 6(5):e1655.
van der Vlugt LE, Labuda LA, Ozir-Fazalalikhan A, Lievers E, Gloudemans AK, Liu KY, Barr TA, SparwasserT, Boon L, Ateba Ngoa U, Ngoune Feugap E, Adegnika AA, Kremsner PG, Gray D, Yazdanbakhsh M, Smits HH. 2012. Schistosomes induce regulatory features in human and mouse CD1dhiB cells: inhibition of allergic inflammation by IL-10 and regulatory T cells. PLoS One, 7(2): e30883.
Hussaarts L, van der Vlugt LE, Yazdanbakhsh M, Smits HH. 2011. Regulatory B-cell induction by helminths: implications for allergic disease. J Allergy Clin Immunol., 128:733-9. Review.
Smits HH, Everts B, Hartgers FC, Yazdanbakhsh M. 2010. Chronic helminth infections protect against allergic diseases by active regulatory processes. Curr Allergy Asthma Rep., 10:3-12. Review.
Wammes LJ, Hamid F, Wiria AE, de Gier B, Sartono E, Maizels RM, Luty AJ, Fillié Y, Brice GT, Supali T, Smits HH, Yazdanbakhsh M. 2010. Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparum. Eur J Immunol., 40:437-42.
Everts B, Perona-Wright G, Smits HH, Hokke CH, van der Ham AJ, Fitzsimmons CM, Doenhoff MJ, van der Bosch J, Mohrs K, Haas H, Mohrs M, Yazdanbakhsh M, Schramm G. 2009. Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses. J Exp Med. 206:1673-80.
Smits HH*, Gloudemans AK*, van Nimwegen M, Willart MA, Soullié T, Muskens F, de Jong EC, Boon L, Pilette C, Johansen FE, Hoogsteden HC, Hammad H, Lambrecht BN. 2009. Cholera toxin B suppresses allergic inflammation through induction of secretory IgA. Mucosal Immunol. 2:331-9.
Smits HH, Yazdanbakhsh M. 2007. Chronic helminth infections modulate allergen-specific immune responses: Protection against development of allergic disorders? Ann Med., 39:428-39. Review.
Smits HH, Hammad H, van Nimwegen M, Soullie T, Willart MA, Lievers E, Kadouch J, Kool M, Kos-van Oosterhoud J, Deelder AM, Lambrecht BN, Yazdanbakhsh M. 2007. Protective effect of Schistosoma mansoni infection on allergic airway inflammation depends on the intensity and chronicity of infection. J Allergy Clin Immunol. 120:932-40.
Leids Universitair Medisch Centrum
2333 ZA Leiden
Tel: +31 71 526 5070
2300 RC Leiden