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Zou Xiang research group

Mast cells as targets for immunotherapy and vaccination

Our research interest focuses on the two functioning arms of mast cells, i.e. their classical role in allergy and the more recently appreciated roles in innate and adaptive immunity.

Mast cells are classically defined as important effector cells in allergic disorders. In allergy, multivalent antigens bind and crosslink IgE molecules bound to the high-affinity IgE-receptor (Fc-epsilon receptor) expressed on mast cells, resulting in allergic inflammation through the release of proinflammatory mediator molecules. It should be emphasized that mast cells also express receptors for IgG and signalling through these Fc-gamma receptors shapes the life and career of these cells as well. We are currently studying the effect of a particular Fc-gamma receptor, i.e. FcgammaRIIb, on mast cell biology. This low affinity receptor binds IgG in the form of antigen-IgG immune-complexes. Co-crosslinking of FcgammaRIIb with activatory receptors by immune-complexes dampens cellular activation. Therefore FcgammaRIIb is critical for down-modulating immune responses, providing a mechanism to limit the duration of immune responses that may otherwise lead to allergy. Our aim is to study the effects of the interaction between FcgammaRIIb and immune-complexes composed of allergen and IgG on the regulation of allergic inflammation as well as therapeutic interventions such as antigen-specific immunotherapy.

More recently, the importance of mast cells has been extended beyond the scope of allergy. They secrete a large spectrum of cytokines and chemokines which play a central role in orchestrating both the innate and adaptive immunity. Mast cell activators are demonstrated to be powerful adjuvants which facilitate humoral immune responses. The mechanism is suggested to involve the inflammatory mediators released by mast cells, which in this way promote dendritic cell maturation and migration. We hypothesized that conventional mucosal adjuvants may also exert their adjuvanticity by activating mast cells, or mast cell activation can be exploited as a novel strategy for designing adjuvants with better potency. Our aim in this project is to design new adjuvant cocktails that may activate mast cells and provide better adjuvanticity.

List of publications

Bruhn S*, Y Fang*, F Barrenäs, M Gustafsson, H Zhang, A Konstantinell, A Krönke, B Sönnichsen, A Bresnick, N Dulyaninova, H Wang, Y Zhao, J Klingelhöfer, N Ambartsumian, MK Beck, C Nestor, E Bona, Z Xiang#, M Benson#. A generally applicable translational strategy identifies S100A4 as a candidate gene in allergy. Science Translational Medicine. 2014; 6:218.
#These authors share the senior authorship.

 

Sun JB*, Xiang Z*, Smith KGCS, Holmgren J. Important Role for FcγRIIB on B Lymphocytes for Mucosal Antigen-Induced Tolerance and Foxp3+ Regulatory T Cells. Journal of Immunology. 2013;191:4412.
*These authors contributed equally.

 

Fang, Y., T. Zhang, L. Lidell, X. Xu, N. Lycke, and Z. Xiang. 2013. The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcgammaRIIIA and augments anti-HPV immunity after nasal immunization. Mucosal Immunol. doi: 10.1038/mi.2013.16.

 

Ren W, K Lagerstedt, O Grimsholm, A Stern, JB Sun, Y Fang, Z Xiang, IL Mårtensson. 2013. Uncoupling of natural IgE production and CD23 surface expression levels. Plos One. doi:10.1371/journal.pone.0062851.

 

Fang Y, Larsson L, Bruhns P, Xiang Z. Apoptosis of mouse mast cells is reciprocally regulated by the IgG receptors FcgRIIB and FcgRIIIA. Allergy 2012; 67: 1233–1240.

 

Fang Y, L Larsson, J Mattsson, N Lycke, and Z Xiang. Mast cells contribute to the mucosal adjuvant effect of CTA1-DD after IgG-complex formation. J. Immunol. 2010; 185(5):2935-41.

 

Wang H, Mobini R, Fang Y, Barrenäs F, Zhang H, Xiang Z, Benson M. Allergen-challenge of PBMCs from patients with seasonal allergic rhinitis increases IL-17RB, which regulates basophil apoptosis and degranulation. Clin Exp Allergy. 2010; 40(8):1194-202

 

Brownlie, R.J., K.E. Lawlor, H.A. Niederer, A.J. Cutler, Z. Xiang, M.R. Clatworthy, R.A. Floto, D.R. Greaves, P.A. Lyons, and K.G. Smith. Distinct cell-specific control of autoimmunity and infection by FcgRIIb. J. Exp. Med. 2008; 205(4):883-95.

 

Karlberg M, Xiang Z, Nilsson G. FcgammaRI-Mediated Activation of Human Mast Cells Promotes Survival and Induction of the Pro-survival Gene Bfl-1. J. Clin. Immunol. 2008; 28(3):250-5.

 

Xiang Z*, AJ Cutler*, RJ Brownlie, K Fairfax, KE Lawlor, E Severinson, EU Walker, RA Manz, DM Tarlinton, and KGC Smith, FcgRIIb controls bone marrow plasma cell persistence and apoptosis. Nat. Immunol., 2007; 8(4): 419-29. *These authors contributed equally.

 

Contact

Zou Xiang, PhD
Mucosal Immunobiology and Vaccine Center
Institute of Biomedicine
Department of Microbiology and Immunology

Visiting address:
40530 Gothenburg, Sweden
Medicinaregatan 7A

Postal address:
Box 435

Phone:
+46 31 7866322

Fax:
+46 31 7866330

E-mail
 

Group members

Zou Xiang, associate professor, docent
Yu Fang, PhD student, email
 

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2014-01-27
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