Dr. Makio Iwashima

Makio Iwashima, Ph.D.
Associate Professor

Ph.D., Stanford University

Molecular & Cellular Immunologist

Cell biology of T cell subsets

CD4 T lymphocytes play critical roles in immune responses against infections and tumors. The majority of CD4 T lymphocytes are called effector cells. They function in the first line of host defense by producing cytokines, inducing antibody formation, and directly killing infected or transformed cells.  There are now at least four different types of effector CD4 T cells are known to exist.  Each subset has different function.  For example, a recently identified subset called Th9 is now known to play a critical role in immunity against tumors and is also involved in pathogenesis of asthma.  

In addition, there is a small group of CD4 T cells, called regulatory T cells, which plays a pivotal role in suppressing unwanted immune responses against self-antigens.  Decreased numbers of regulatory T cells, or impairment of their function, leads to autoimmune disorders such as Type I diabetes or inflammatory bowel disease.  Conversely, increased numbers of regulatory T cells may contribute to chronic infectious diseases or growth of tumors.

We have developed procedures to isolate and expand or reduce specific fractions of T cells.  The data showed that there are complex communications between T cells and other types of cells in tissue and the blood and the effector/regulatory T cell subsets develop depends on the cells and factors present in their surrounding.  Our main research interest is to elucidate this communication process between T cells and other cells.  The main questions that we address are:

(1) What is the key signal that determines CD4 T cells to become regulatory subset?
(2) What environmental factor(s) control differential development of Th9 cells?
(3) How the balance between regulatory and effector T cells is maintained?

Successful completion of these studies will potentially lead to treatment for autoimmune disorders, enhancement of immune response against tumors, and development of vaccine effective for infants and immunocompromised individuals.

Selected Publications

Singh N., Seki, Y., Takami, M., Baban, B., Chandler, P.R., Khosravi, D., Zheng, X., Takezaki, M., Lee, J.R., Mellor, A.L., Bollag, W.B., and Iwashima, M*.  Enrichment of regulatory CD4+CD25+ T cells by inhibition of Phospholipase D signaling. (2006)  Nature Methods  3(8):629-36.

Singh N., Chandler, P.R., Seki, Y., Baban, B., Takezaki, M., Munn D.H., Larsen, C.P., Mellor, A.L., and Iwashima M*.  Role of CD28 in lethal lymphoproliferative disease in scurfy mice. (2007) Blood  110(4):1199-1206.

Pacholczyk R, Kern J, Singh N, Iwashima M, Kraj P, Ignatowicz L. Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells. (2007)  Immunity 27 (3) 493-504.

Singh, N., Yamamoto, M., Takami, M., Seki, Y., Takezaki, M., Mellor, S.L., and Iwashima, M*., CD4+CD25+ regulatory T cells resist a novel form of CD28-and Fas-dependent p53-induced T cell apoptosis.  (2010)  J. Immunol. 184(1):94-104

Takami M, Love, R., and Iwashima, M*.   TGF-b converts apoptotic stimuli into the signal for Th9 differentiation. (2012) J Immunol. 2012 May 1;188(9):4369-75. Epub 2012 Mar 28. PMC3331903

Shah S, Lowery, E., Braun R.K., Martin A., Huang N., Medina M., Sethupathi P., Seki Y., Takami M., Byrne K., Wigfield C., Love R.B., and Iwashima M*. Cellular basis of tissue regeneration by omentum (2012) PLoS One. 2012;7(6):e38368. PMC3368844

Yamamoto M, Seki Y., Iwai K., Ko I., Martin A., Tsuji N., Miyagawa S., Love RB, and Iwashima M*.  (2013) Cytokine , Mar;61(3):831-41

Iwashima M, Love R. Potential of targeting TGF-β for organ transplant patients.  (2013) Future Med Chem. Mar;5(3):281-9

 

 

 

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