My 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 important effector cells in allergic diseases.They express receptors for immunoglobulins and signalling through these Fc receptors mediates the allergic cellular events. My research is currently focused on the effects of Fcg receptors on mast cell biology by using in vitro and in vivo mouse models. Mouse mast cells express the low affinity Fcg receptors FcgRIIB and FcgRIIIA which bind IgG especially in the form of antigen-IgG immune complexes. We found that aggregation of one of these two receptors by IgG immune complexes, in the absence of the other, induced apoptosis of mouse mast cells. We are currently studying the Fcg receptor-mediated mechanisms for regulating the persistence and homeostasis of tissue mast cells, as well as the implication of Fcg receptor-mediated apoptosis in the treatment of allergies.
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. More recently, mast cells have been implicated in the development of novel vaccine adjuvants by virtue of their potential in secreting a large spectrum of cytokines that favour adaptive immune responses. We are trying to develop new strategies for designing adjuvant formulations that may lead to better immunization efficacy by engaging mast cells and their Fcg receptors.
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. Sci Transl Med. In press. #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. J Immunol. 2013;191:4412. *These authors contributed equally.
Fang, Y., T. Zhang, L. Lidell, X. Xu, N. Lycke, Z. Xiang. 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. 2013; 6:1168.
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. 2013; 8:e62851.
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.
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; 185:2935.
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; 40:1194.
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; 205:883.
Xiang Z*, AJ Cutler*, RJ Brownlie, K Fairfax, KE Lawlor, E Severinson, EU Walker, RA Manz, DM Tarlinton, and KGC Smith, FcRIIb controls bone marrow plasma cell persistence and apoptosis. Nat. Immunol., 2007; 8(4): 419-29 *These authors contributed equally.
Vigorito E, KL Perks, C Abreu-Goodger, S Bunting, Z Xiang, S Kohlhaas, PP Das, EA Miska, A Rodriguez, A Bradley, KGC Smith, C Rada, AJ Enright, KM Toellner, IC MacLennan and M Turner, bic/miR-155 regulates the generation of Ig class switched plasma cells. Immunity. 2007; 27:847.
Xiang Z, Moller C, Nilsson G. IgE-receptor activation induces survival and Bfl-1 expression in human mast cells but not basophils. Allergy. 2006; 61:1040.
Xiang Z, Moller C, Nilsson G. Readministration of IgE is required for repeated passive cutaneous anaphylaxis in mice. Int. Arch. Allergy Immunol. 2006; 141:168.