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 misregulated 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, Lerman YV, 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.