Booki Min, D.V.M., Ph.D.
Associate Staff

Booki Min, D.V.M., Ph.D.

Associate Staff

  • Department of Immunology

  • Lerner Research Institute (NB30)

  • The Cleveland Clinic Foundation

  • 9500 Euclid Avenue

  • Cleveland, Ohio 44195

  • (216) 445-3126

  • (216) 444-8372

Research interest

T cell homeostasis, gd T cells, CD8 T cells, Role of basophils in adaptive immunity

Current program

  • T cell homeostasis and lymphocyte dynamics
  • Biology of basophils and their roles in innate/adaptive immunity

Brief Description

Homeostatic regulation of T lymphocytes is a central mechanism by which the immune system ensures its diversity and functionality. T cell deficiency triggers a proliferative response of T cells that remain within such conditions or that are adoptively transferred into such environments (which is often referred to as homeostatic proliferation or endogenous proliferation). The proliferation is often associated with a differentiation process that generates memory T cells. The resulting memory T cells are thought to play a critical role in the regulation of peripheral homeostasis as well as in the protection against invading pathogens.

There is substantial evidence suggesting that lymphopenia induced immune activation may result in autoimmunity, multiorgan immunopathology, as well as rejection of solid organ transplants. Therefore, understanding the mechanisms regulating T cell proliferation in lymphopenic conditions has fundamental biological importance. Our study aims at defining the mechanisms by which T cell proliferation/differentiation processes are induced and regulated.

How T cells are induced to proliferate without exogenous cognate Ag stimulation? Why it doesn't occur under non-lymphopenic conditions? We have recently reported that different subsets of APCs are involved in proliferation of T cell subsets; namely, naïve and memory CD4 T cell proliferation is completely dependent on interaction with MHC II molecules exclusively expressed on CD11c+ DCs. On the other hand, naïve CD8 T cell proliferation still occurs in the absence of MHC I. Surprisingly, CD8 T cells are capable of interacting with MHC II molecules when MHC I is absent. For details, see Do et al. PNAS (2009). We currently examine cellular mechanism that regulates proliferation in vivo. We are also interested in understanding the contribution of apoptosis of T cells during homeostatic regulation.

Recently, we became interested in gd T cell subsets that are specialized in producing IL-17 under non-inflammatory conditions. We identified that these IL-17+ gd T cells are primarily generated within the thymus during the postnatal period and that TGF b 1 plays the major role in the generation. However, cellular mechanism underlying the in vivo generation of IL-17+ gd T cells as well as their immunologic roles as 'innate IL-17-producers' remain poorly understood. We are actively pursuing this issue.

Another project that we recently initiated is to examine T cell homeostasis within nonlymphoid tissues, the CNS during acute and persistent virus infection. Our lab teamed with Drs. Steve Stohlman and Conni Bergmann (Neuroscience Dept, CCF), and investigate cellular mechanisms of T cell retention within the CNS during the JHMV infection. More specifically, we will determine whether viral Ag presentation induces CD8 T cell retention in the CNS during persistent infection. Moreover, we will test how CD4 T cells contribute to the survival and the retention of CD8 T cells in the CNS during persistent infection.

Last project that we investigate is to examine in vivo roles of basophils. Basophils have recently been studied by many investigators, and their roles as immune effectors as well as modulators continue to increase. We are particularly interested in mechanism that mobilizes circulating basophils into the lymphoid tissues. This will be an interesting topic because it is believed that basophils which that enter the LN promote the development of Th2 immune responses in vivo. However, we recently reported that it is not always the case; i.e., basophils may be dispensable for Th2 immunity under certain circumstances. We are in process of dissecting the processes of in vivo migration of circulating basophils and their participation during Th2-related immune responses.

Investigators

  • Jeong-Su Do, Ph.D., Postdoctoral fellow
  • Sohee Kim, Technician
  • Hwang, Mi-hyun, Postdoctoral Fellow
  • Anabelle Visperas, Graduate student

Collaborators

  • Graham LeGros, Ph.D., Malaghan Medical Research Institute, New Zealand
  • Pamela Fink, Ph.D., University of Washington
  • John Letterio, M.D., Case Western Reserve University
  • Marc Hellerstein, M.D. Ph.D., University of California , Berkeley
  • Angel Lopez, Ph.D., Centre for Cancer Biology, South Australia
  • Xiaoxia Li, Ph.D., CCF
  • Stephen Stohlman, Ph.D., CCF
  • Cornelia Bergmann, Ph.D., CCF
  • Jeong-Su Do Ph.D.
  • Research Associate
  • Location:NB3-48
  • doj@ccf.org
  • (216) 445-3083
  • Michael Freeman Ph.D.
  • Research Associate
  • Location:NB3-48
  • freemam5@ccf.org
  • (216) 445-3083
  • Mihyun Hwang
  • Postdoctoral Fellow
  • Location:NB3-37A
  • hwangm@ccf.org
  • (216) 445-3083
  • Anabelle Visperas
  • Graduate Student
  • Location:NB3-37
  • vispera@ccf.org
  • (216) 445-3083

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2012

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. AOP.

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.

Min, B. M. A. Brown, and G. Le Gros. (2012). Understanding the roles of basophils: breaking dawn. Immunology AOP.

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, R. L. O’brien, and B. Min. (2012). CD4 T cells enhance the generation of IL-17+ γδ T cells. Immunol. Cell. Biol. AOP.

2011

Min, B. (2011). Inside Blood. Deleting Mcl-1 in mast cells: getting two birds with one stone. Blood 118:6729-2730.

Bosch, X. F. Lozano, R. Cervera, M. Ramos-Casals, and B. Min. (2011) Basophils, IgE and autoantibody-mediated kidney disease. J. Immunol. 186:3083-6090.

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+ γδT cells. J. Immunol. 186:4546-4550.

van Panhuys, N., M. Prout, E. Forbes, B. Min, W. E. Paul, and G. Le Gros. (2011). Basophils are the major producers of IL-4 during primary helminth infection. J. Immunol. 186:2719-2728.

Min, B. (2010). Commentary. Mice that conditionally lack basophils: at last! J. Clin. Invest. 120: 2648-2651.

Min, B. (2010). Basophils induce Th2 immunity: is this final answer? Virulence 1:399-401.

Forbes, E., N. van Panhuys, B. Min, and G. Le Gros. (2010). Differential requirements for IL-4/STAT6 signalling in CD4 T cell fate determination and Th2 immune effector responses. Immunol. Cell. Biol. 88: 240-243.

Gulen, M.F, Z. Kang, K. Bulek, C. Z. Altuntas, M.J. McGeachy, J. Do, H. Xiao, B. Min, V.K. Tuohy, D.J. Cua, and X. Li. (2010). SIGIRR, a negative regulator of IL-1R-TLR suppresses Th17 expansion through IL-1-induced mTOR-mediated cell proliferation. Immunity 32: 54-66.

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., 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 γδ T cells in the thymus occurs via a TGF1-dependent mechanism. J. Immunol. 184: 1675-1679.

Bulek, K., S. Swaidani, J. Qin, Y. Lu, F. Gulen, B. Min, R. A. Kastelein, M. Aronica, M. Kosz-Vnenchak, and X. Li. (2009). The essential role of SIGIRR in regulation of Th2 immune response. J. Immunol. 182: 2601-2609.

Do, J. and B. Min. (2009). IL-15 produced and trans-presented by DCs underlies homeostatic competition between CD8 and γδ 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.

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.

T. Shen, S. Kim, L. Wang, C. Lantz, J. F. Urban Jr, G. Le Gros, B. Min. (2008). Parasite infection induced basophil production requires T cell production of IL-3 but IL-3 is dispensable for in vivo basophil survival. Int. Immunol. 20: 1201-1209.

Wang, L., N. van Panhuys, J. Hu-Li, S. Kim, G. Le Gros, and B. Min. (2008). Blimp-1 induced by IL-4 plays a critical role in suppressing IL-2 production in activated CD4 T cells. J. Immunol. 181: 5249-5256.

Sharma, P., R. Chakraborty, L. Wang, B. Min, M. L. Tremblay, T. Kawahara, J. D. Lambeth, and S. J. Haque. (2008). Redox regulation of interleukin-4 signaling. Immunity 29: 551-564.

Lantz, C.S., B. Min, M. Tsai, G. Dranoff, and S. J. Galli. (2008). IL-3 is required for the increase in blood basophils during nematode infection in mice, but not for basophil IgE-dependent intra-cellular IL-4 production. Lab. Invest. 88: 1134-1142.

Min, B. (2008). Basophils: what they ‘can do’ and what they ‘actually do’. Nat. Immunol. 9: 1333-1339.

Min, B. and W. E. Paul. (2008). Basophils and type 2 immunity. Curr. Opin Hematol. 15: 59-63.

Min, B. and W. E. Paul. (2008). News & Views. Basophils: in the spotlight at last. Nat. Immunol. 9: 223-225.

Oh, K., T. Shen, G. Le Gros, and B. Min. (2007). Induction of Th2 immunity by murine basophils reveals a novel immunoregulatory role of basophils. Blood 109: 2921-2927.

Do, J., G. Foucras, A. F. Schenk, M. Shaw, G. Nunez, W. E. Paul, and B. Min. (2011). Both exogenous commensal and endogenous self antigens stimulate T cell proliferation under lymphopenic conditions. Cell. Immunol. In Press.

Min, B. (2011). Inside Blood. Deleting Mcl-1 in mast cells: getting two birds with one stone. Blood In Press.

Min, B. M. A. Brown, and G. Le Gros. (2011). Understanding the roles of basophils: breaking dawn. Immunology In Press.

Do, J., A. Visperas, K. Oh, S. A. Stohlman, and B. Min. (2011). Memory CD4 T cells induce selective expression of IL-27 in CD8+ DC and regulate homeostatic naïve T cell proliferation. J. Immunol. In Press .

Bosch, X. F. Lozano, R. Cervera, M. Ramos-Casals, and B. Min. (2011) Basophils, IgE and autoantibody-mediated kidney disease. J. Immunol. In Press.

Do, J., A. Visperas, R. L. O’brien, and B. Min. (2011). CD4 T cells enhance the generation of IL-17+ gd T cells. Immunol. Cell. Biol. In Press.

van Panhuys, N., M. Prout, E. Forbes, B. Min, W. E. Paul, and G. Le Gros. (2011). Basophils are the major producers of IL-4 during primary helminth infection. J. Immunol. 186:2719-2728.

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. In Press.

Immunity Immunology & Cell Biology The Journal of Immunology Virulence

2010

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 TGF b 1-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 .

Gulen, M.F., Z. Kang, K. Bulek, W. Youzhong, T.W. Kim, Y. Chen, C.Z. Altuntas, K. Bak-Jenson, M.J. McGeachy, J-s. Do, H. Xiao, G.M. Delgoffe, B. Min, J.D. Powell, V.K. Tuohy, D.J. Cua, and X. Li. (2010) . SIGIRR, a negative regulator of IL-1R-TLR suppresses Th17 expansion through IL-1-induced mTOR-mediated cell proliferation. Immunity . 32: 54-66.

Forbes, E., N. van Panhuys, B. Min, and G. Le Gros. ( 2010 ). Differential requirements for IL-4/STAT6 signalling in CD4 T cell fate determination and Th2 immune effector responses. Immunol. Cell. Biol. 88:240-243.

Min, B. (2010) Editorial. Th2 immunity: a step closer to completion. Immunol. Cell. Biol. 88:235.

Min, B. (2010). Commentary. Mice that conditionally lack basophils: at last! J. Clin. Invest. In Press.

Min, B. (2010). Basophils induce Th2 immunity inducers: is this final answer? Virulence. In Press.

Current Cover Cover Cover

2009

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.

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.

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.

Bulek, K., S. Swaidani, J. Qin, Y. Lu, F. Gulen, B. Min, R. A. Kastelein, M. Aronica, M. Kosz-Vnenchak, and X. Li. (2009) . The essential role of SIGIRR in regulation of Th2 immune response. J. Immunol. 182: 2601-2609.

2008

Min, B. (2008) . Basophils: what they ‘can do' and what they ‘actually do'. Nat. Immunol . 9: 1333-1339.

Lantz, C.S., B. Min, M. Tsai, G. Dranoff, and S. J. Galli. (2008) . IL-3 is required for the increase in blood basophils during nematode infection in mice, but not for basophil IgE-dependent intra-cellular IL-4 production. Lab. Invest . 88: 1134-1142.

Sharma, P., R. Chakraborty, L. Wang, B. Min, M. L. Tremblay, T. Kawahara, J. D. Lambeth, and S. J. Haque. (2008) . Redox regulation of interleukin-4 signaling. Immunity 29: 551-564.

Wang, L., N. van Panhuys, J. Hu-Li, S. Kim, G. Le Gros, and B. Min. ( 2008) . Blimp-1 induced by IL-4 plays a critical role in suppressing IL-2 production in activated CD4 T cells. J. Immunol . 181: 5249-5256.

T. Shen, S. Kim, L. Wang, C. Lantz, J. F. Urban Jr, G. Le Gros, B. Min. (2008) T cell -derived IL-3 plays key role in parasite infection - induced basophil production but is dispensable for in vivo basophil survival. Int. Immunol . 20: 1201-1209.

Min, B. and W. E. Paul. (2008) . News & Views. Basophils: in the spotlight at last. Nat. Immunol . 9: 223-225.

Min, B. and W. E. Paul. (2008) . Basophils and type 2 immunity. Curr. Opin Hematol . 15: 59-63.

S1074-7613(09)X0011-7 Cover Image European Journal of Immunology