Guoxing Zheng, PhD
Associate Professor (RT)
Department of Biomedical Sciences
Contact
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1601 Parkview Avenue, Rockford, IL 61107
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About
Mechanisms of adaptive immune tolerance
We are interested in understanding the cellular and molecular mechanisms involved in either breaking or inducing T cell non-responsiveness to specific antigens. Using a method of protein transfer we are able to add lipid-derivatized immune-stimulating proteins, including T cell costimulators and cytokines, directly onto the surfaces of T cells, dendritic cells, and tumor cells ex vivo and in situ. This creates novel, and enhanced, interactions between these cell types and may ultimately allow the breaking of tumor tolerance. This line of work has led to the design of novel cellular cancer vaccines and therapeutic T cells for both active and passive cancer immunotherapies, respectively. We are also interested in defining the conditions of antigen presentation that potentiate adaptive T cell tolerance. This line of research has led to the finding that antigen immunization under glucocorticoid-induced immunosuppression can attenuate established memory responses by T and B cells. In particular, the glucocorticoid dexamethasone can function as a tolerogenic adjuvant by preferentially inducing apoptosis of dendritic cells (cDCs and pDCs), effector CD4+ T cells, and B-2 cells; whereas CD11cloCD40loCD86hiMHCIIlo macrophages, CD4+Foxp3+ Treg cells, and IL-10+ B-1 cells are relatively protected. As a result, Ag immunization in the presence of Dex raises Ag-specific Treg and B-1 cells while blocking the recall responses of Teff and B-2 cells, which leads to adaptive tolerance. The Treg cells represent the principal tolerizing effectors raised by SI, whereas the role the B-1 cells is currently being investigated. A hypothesis we are currently testing, in collaboration with Dr. Aoshuang Chen, is whether vaccines for common inflammatory or autoimmune diseases, such as atherosclerosis, type 1 diabetes, and type 2 diabetes may be designed to consist of dexamethasone and a disease-specific antigen(s).
Selected Publications
Cutting edge: Dexamethasone potentiates the responses of both regulatory T cells and B-1 cells to antigen immunization in the ApoE(-/-) mouse model of atherosclerosis. Chen A, Geng Y, Ke H, Constant L, Yan Z, Pan Y, Lee P, Tan I, Williams K, George S, Munirathinam G, Reardon CA, Getz GS, Wang B, Zheng G. J Immunol. 2014 Jul 1;193(1):35-9. doi: 10.4049/jimmunol.1302469. Epub 2014 Jun 4. PMID: 24899497
Palmitate-derivatized human IL-2: a potential anticancer immunotherapeutic of low systemic toxicity. Chou SH, Shetty AV, Geng Y, Xu L, Munirathinam G, Pipathsouk A, Tan I, Morris T, Wang B, Chen A, Zheng G. Cancer Immunol Immunother. 2013 Mar;62(3):597-603. doi: 10.1007/s00262-012-1364-8. Epub 2012 Nov 4. PMID: 23124508
Dexamethasone promotes tolerance in vivo by enriching CD11clo CD40lo tolerogenic macrophages. Zheng G, Zhong S, Geng Y, Munirathinam G, Cha I, Reardon C, Getz GS, van Rooijen N, Kang Y, Wang B, Chen A. Eur J Immunol. 2013 Jan;43(1):219-27. doi: 10.1002/eji.201242468. Epub 2012 Nov 7. PMID: 23001956
Kang Y, Xu L, Wang B, Chen A, Zheng G. Cutting edge: Immunosuppressant as adjuvant for tolerogenic immunization. J Immunol. 2008 Apr 15;180(8):5172-6. doi: 10.4049/jimmunol.180.8.5172. PMID: 18390698; PMCID: PMC2377418.