Unlike cells within solid tissues, circulating lymphocytes and other leukocytes continuously migrate and relocate during the course of immune reactions. A subset of integrins (LFA-1, Mac-1, and VLA-4) are expressed on immune cells and play a major role in regulating recruitment of immuno-competent cells to normal or damaged and infected tissues. Under a wide range of pathologic conditions such as autoimmune disease, chronic inflammation, and transplantation rejection, integrin activations are mis-regulated resulting in abnormal leukocyte trafficking, and direct damage to the vasculature and the underlying host tissue.
Understanding how T cells and neutrophils home to and migrate within tissues is a major focus of our research.
M. Kim, C.V. Carman, and T.A. Springer. 2003. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301(5640), 1720-1725.
N.A. Morin, P.W. Oakes, Y.-M. Hyun, D. Lee, E.Y. Chin, M.R. King, T.A. Springer, M. Shimaoka, J.X. Tang, J.S. Reichner, and M. Kim. 2008. Non-muscle myosin heavy chain-IIA (My-H9) mediates integrin LFA-1 de-adhesion during T lymphocyte migration. J. Exp. Med. 205(1):195-205.
G.F. Elphick, P.P. Sarangi, Y-M Hyun, J.A. Hollenbaugh, A. Ayala, W.L. Biffl, H-L Chung, A.R. Rezaie, J.L. McGrath, D.J. Topham, J.S. Reichner, and M. Kim. 2009. Recombinant human activated protein C inhibits integrin-mediated neutrophil migration. Blood 113(17): 4078-85 .
CM Baker, WA Comrie, Y-M Hyun, C Fedorchuk, C Brakebusch, J Miller, M Meier-Schellersheim, and Kim M. 2012. Opposing roles for RhoH GTPase during T cell migration and activation. Proc Natl Acad Sci U S A Jun 26;109(26):10474-9.
Y-M Hyun, R Sumagin, P Sarangi, M Overstreet, C Baker, D Fowell, I Sarelius, and M. Kim. 2012. Uropod elongation is a common final step in leukocyte extravasation through inflamed vessels. J. Exp. Med. Jul 2;209(7):1349-62.
Sarangi PP, LermanYV, Lim K, Hyun Y-M, Falkner KL, Pietropaoli AP, Lacy-Hulbert A, Sonnenberg A, and Kim M. 2014. Sepsis lethality through exacerbated tissue infiltration and TLR-induced cytokine production by neutrophils is dependent on integrin α3β1. Blood Dec 4;124(24):3515-23.
Xu Y, Hyun YM, Lim K, Lee H, Cummings RJ, Gerber SA, Bae S, Cho TY, Lord EM, and Kim M. 2014. Optogenetic control of chemokine receptor signal and T-cell migration. Proc Natl Acad Sci U S A Apr 29;111(17):6371-6.
Lim K, Hyun YM, Lambert-Emo K, Capece T, Bae S, Miller R, Topham DJ, and Kim M. 2015. Neutrophil trails guide influenza-specific CD8+ T cells in the airways. Science Sep 4; 349 (6252): aaa4352.