Department of Inflammation and Immunity
Booki Min, D.V.M., Ph.D.
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 445-3126
T lymphocytes (T cells) are the main immune cells that play a central role in protecting us from pathogens. However, T cell responses must be tightly controlled, because uncontrolled responses often result in inflammatory diseases in human. One key mechanism that regulate immune responses is a subset of T cells known as regulatory T cell (Treg). Treg are essential component of the immune system. Treg suppress immune responses, diminishing inflammation. Defects in Treg generation or function result in systemic autoimmune diseases in human and mouse leading to premature death. Therefore, understanding Treg biology is an important subject of investigation. In my laboratory, we investigate factors that regulate Treg function. If Treg functions are too strong, then immune system is overly suppressed. On the other hand, if Treg functions are too weak, then the immune system is overly activated.
There is accumulating evidence that chronic inflammatory disorders such as autoimmune diseases and asthma are manifested by dysregulated Treg functions. Using mouse model of chronic inflammation models, we examine both cellular and molecular mechanisms by which Treg functions can be modulated. In particular, we use: Experimental Autoimmune Encephalomyelitis, a mouse model for human Multiple Sclerosis; T cell-induced colitis, a mouse model for human Inflammatory Bowel Disease; and allergic airway inflammation, a mouse model for human asthma. Our ongoing studies have identified that a soluble immune mediator called “Interleukin-27” is essential for Treg to properly regulate inflammation. Using a newly developed genetically engineered mouse model in which the receptor for “Interleukin-27” is selectively missing only on Treg, we found that these animals are highly susceptible to every inflammatory models tested. Furthermore, if Treg are pre-stimulated with “Interleukin-27”, they become highly potent suppressor cells. This is especially exciting because Treg infusion therapy is currently being implemented in treating chronic inflammatory diseases in human.
In other words ...
- Roles of regulatory T cells in chronic inflammatory diseases
DongKyun Kim Ph.D.
Postdoctoral Research Fellow
Thi Hong Nga Le Ph.D.
Postdoctoral Research Fellow
Quang Tam Nguyen Ph.D.
Postdoctoral Research Fellow
Jang, E.J., S. Kim, D. Kim, T.H. Le, K. Keslar, M.A. Aronica, B. Min. (2017). Lung infiltrating Foxp3+ regulatory T cells are quantitatively and qualitatively different during eosinophilic and neutrophilic allergic airway inflammation but essential to control the inflammation. J. Immunol. In Press.
Do, J., D. Kim, S. Kim, A. Valentin-Torres, N. Dvorina, E. Jang, V. Nagarajavel, T. DeSilva, X. Li, A. Ting, D. Vignali, S. Stohlman, W. Baldwin, and B. Min. (2017). Treg specific IL-27Ra deletion uncovers a key role for IL-27 in Treg function to control autoimmunity. Proc. Natl. Acad. Sci. USA. 114:10190-10195.
Min, B. (2017). Heterogeneity and stability in Foxp3+ regulatory T cells. J. Interferon Cytokine Res. Epub ahead of print.
Do, J., S. Kim, K. Kesler, E. Jang, E. Huang, R. L. Fairchild, T. T. Pizarro, and B. Min. (2017). γδ T cells coexpressing gut homing α4β7 and αE integrins define a novel subset promoting intestinal inflammation. J. Immunol. 198:908-915.
Martin, B. N., T. Herjan, M. F. Gulen, K. Bulek, B. Min, and X. Li. (2016). T cell-intrinsic ASC critically promotes Th17-mediated experimental autoimmune encephalomyelitis. Nat. Immunol. 17: 583-592.
Do, J., A. Visperas, M. Freeman, E. Jang, S. Kim, B. Malissen, and B. Min. (2016). gd T cells support gut antigen reactive colitogenic effector T cell generation by enhancing antigen presentation by CD11b+ DCs in the mesenteric LN. Eur. J. Immunol. 46:340-346.
Do, J., A. Visperas, Y. O. Sanogo, J. J. Bechtel, N. Dvorina, S. Kim, E. Jang, S. A. Stohlman, B. Shen, R. L. Fairchild, W. M. Baldwin III, D. A. Vignali, and B. Min. (2016). An IL-27/LAG3 axis enhances Foxp3+ regulatory T cell suppressive function and therapeutic efficacy. Mucosal Immunol. 9:137-145.
Datta, S., N. Barrera, P. J. Pavicic, C. Zhao, M. Freeman, B. Min, and T. Hamilton. (2015). cEBP homologous protein expression in macrophages regulates the magnitude and duration of IL-6 expression and dextran sodium sulfate colitis. J. Interferon Cytokine Res. 35:785-794.
Do, J., W. M. Baldwin III, and B. Min. (2014). Spontaneous proliferation of H-2M-/- CD4 T cells results in unusual acute hepatocellular necrosis. PLoS One9(10): e110516. doi:10.1371.
Hwang, M., T. W. Phares, D. R. Hinton, S. A. Stohlman, C. C. Bergmann, and B. Min. (2015). Distinct effects of CD4 T cells on establishment of primary versus recall CD8 T cell responses during viral encephalomyelitis. Immunology144:374-386.
Visperas, A., J. Do, and B. Min. (2014). Cellular factors targeting APCs to modulate adaptive T cell immunity. J. Immunol. Res. 2014:750374. Epub 2014 Jul 14.
Visperas, A., B. Shen, and B. Min. (2014). gd T cells restrain extrathymic development of Foxp3+ inducible regulatory T cells via IFNg. Eur. J. Immunol. 44:2448-2456.
Do, J., K. Asosingh, W. M. Baldwin, and B. Min. (2014). Cutting Edge: IFNg signaling in non-T cell targets regulates T cell-mediated intestinal inflammation through multiple mechanisms. J. Immunol. 192:2537-2541.
Visperas, A., J. Do, K. Bulek, X. Li, and B. Min. (2014). IL-27, targeting antigen presenting cells, enhances Th17 differentiation and inflammation by upregulating Th17 promoting cytokine production. Mucosal Immunol.7:625-633.
Do, J., A. Visperas, M. L. Freeman, Y. Iwakura, M. Oukka, and B. Min. (2014). Colitogenic effector T cells: roles of gut homing integrin, gut antigen specificity and gd T cells. Immunol. Cell. Biol. 92:90-98.
Rao, K. N., C. Smuda, G. D. Gregory, B. Min, and M. A. Brown. (2013). Ikaros limits basophil development by suppressing C/EBPa expression. Blood122:2572-2581.
Do, J., A. Valujskikh, D. A. A. Vignali, R. L Fairchild, and B. Min. (2012). An unexpected role for MHCII-peptide complexes in shaping CD8 T cell expansion and differentiation in vivo. Proc. Natl. Acad. Sci. USA 109:12698-12703.
Zizhen, K., S. Swaidani, W. Yin, C. Wang, J. L. Barlow, M. F. Gulen, K. Bulek, J. Do, M. Aronica, A. N. McKenzie, B. Min, and X. Li. (2012). Epithelial cell-specific Act1 adaptor mediates IL-25-dependent helminth expulsion through expansion of Lin(-)c-Kit(+) innate cell population. Immunity 36:821-833.
Phares, T. W., S. A. Stohlman, M. Hwang, B. Min, D. R. Hinton, and C. C. Bergmann. (2012). CD4 T cells promote CD8 T cell immunity at the priming and effector site during viral encephalitis. J. Virol. 86:2416-2427.
Do, J., G. Foucras, A. F. Schenk, M. Shaw, G. Nunez, W. E. Paul, and B. Min. (2012). Both exogenous commensal and endogenous self antigens stimulate T cell proliferation under lymphopenic conditions. Cell. Immunol. 272:117-123.
Do, J., A. Visperas, R. L. O’brien, and B. Min. (2012). CD4 T cells enhance the generation of IL-17+ gd T cells. Immunol. Cell. Biol. 90:396-403.
Do, J., A. Visperas, K. Oh, S. A. Stohlman, and B. Min. (2012). Memory CD4 T cells induce selective expression of IL-27 in CD8+ DC and regulate homeostatic naïve T cell proliferation. J. Immunol. 188:230-237.
Do, J., A. Visperas, C. Dong, W. Baldwin, and B. Min. (2011). Cutting Edge: Generation of colitogenic Th17 CD4 T cells is enhanced by IL-17+ gd T cells. J. Immunol. 186:4546-4550.
Do, J., P.J. Fink, L. Li, R. Spolski, J. Robinson, W. J. Leonard, J. J. Letterio, and B. Min. (2010). Cutting Edge: Spontaneous development of IL-17-producing gd T cells in the thymus occurs via a TGFb1-dependent mechanism. J. Immunol. 184: 1675-1679.
Kim, S., M. Prout, H. Ramshaw, A. F. Lopez, G. Le Gros, and B. Min. (2010). Cutting Edge: Basophils are transiently recruited to the draining lymph node during helminth infection via IL-3 but infection-induced Th2 immunity develops without basophil LN recruitment or IL-3. J. Immunol. 184: 1143-1147.
Do, J. and B. Min. (2009). Differential requirements of MHC and of DCs for endogenous proliferation of different T-cell subsets in vivo. Proc. Natl. Acad. Sci. USA 106: 20394-20398.
Do, J. and B. Min. (2009). IL-15 produced and trans-presented by DCs underlies homeostatic competition between CD8 and gd T cells in vivo. Blood 113: 6361-6371.
Kim, S., T. Shen, and B. Min. (2009). Basophils can directly present or cross-present Ag to CD8 lymphocytes and alter CD8 T cell differentiation into IL-10-producing phenotypes. J. Immunol. 183: 3033-3039.