Cutting Edge: Stimulation of dopamine D4 receptors induce T cell quiescence by up-regulating Kruppel-like factor-2 expression through inhibition of ERK1/ERK2 phosphorylation.
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.
Sarkar
Chandrani
C
Signal Transduction and Biogenic Amines Laboratory, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata 700026, India.
Das
Shamik
S
Chakroborty
Debanjan
D
Chowdhury
Uttio Roy
UR
Basu
Biswarup
B
Dasgupta
Partha Sarathi
PS
Basu
Sujit
S
D049109:Cell Proliferation / Q000187:drug effects; D004298:Dopamine / Q000276:immunology / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D010766:Phosphorylation; D050638:Receptors, Dopamine D4 / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D051741:Kruppel-Like Transcription Factors; D050638:Receptors, Dopamine D4; D048049:Extracellular Signal-Regulated MAP Kinases; D004298:Dopamine