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Cutting Edge: Stimulation of Dopamine D₄ Receptors Induce T Cell Quiescence by Up-Regulating Krüppel-Like Factor-2 Expression through Inhibition of ERK1/ERK2 Phosphorylation¹

Chandrani Sarkar^2,*, Shamik Das^2,*, Debanjan Chakroborty^2,*, Uttio Roy Chowdhury^*, Biswarup Basu^*, Partha Sarathi Dasgupta^3,* and Sujit Basu^3,,

^* Signal Transduction and Biogenic Amines Laboratory and Department of Medical Oncology, Chittaranjan National Cancer Institute, Kolkata, India; and Mayo Clinic Cancer Center and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905

The neurotransmitter dopamine (DA) is an important regulator of human T cell functions. Although it has been observed that DA, by acting through the D₁/D₅, D₂, and D₃ receptors, can activate resting T cells by stimulating the release of cytokines and the expression of surface integrins and also inhibit the proliferation of activated T cells by down-regulating nonreceptor tyrosine kinases, there is not yet a report indicating the functional significance of the D₄ DA receptors present in these cells. The present work, for the first time, demonstrates that the stimulation of D₄ DA receptors in human T cells induces T cell quiescence by up-regulating lung Krüppel-like factor-2 expression through the inhibition of ERK1/ERK2 phosphorylation. These results reveal a new link between the nervous system and T cell quiescence and indicate that D₄ DA receptor agonists may have a therapeutic value in diseases with uncontrolled T cell proliferation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Defense Research and Development Organization, Government of India Grant LSRB-24/EPB (to P.S.D.) and National Institutes of Health Grant CA118265 (to S.B.).

² C.S., S.D., and D.C. equally contributed to this work.

³ Address correspondence and reprint requests to Dr. Partha Sarathi Dasgupta, Signal Transduction and Biogenic Amines Laboratory, 37 S.P. Mukherjee Road, Kolkata 700026, India. E-mail address: partha42002{at}yahoo.com or Dr. Sujit Basu, Mayo Clinic Cancer Center and Department of Biochemistry and Molecular Biology, 200 First Street Southwest, Guggenheim 1494, Mayo Clinic, Rochester, MN 55905. E-mail address: basu.sujit{at}mayo.edu

⁴ Abbreviations used in this paper: DA, dopamine; KLF, Krüppel-like factor; 7-AAD, 7-aminoactinomycin D.