Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells.
Interleukin 22 (IL-22) is a member of the IL-10 cytokine family that is involved in inflammatory and wound healing processes. Originally considered a T helper type 1 (T(H)1)-associated cytokine, IL-22 has since been shown to be produced mainly by IL-17-producing helper T cells (T(H)-17 cells). Here we describe a previously uncharacterized IL-22-producing human helper T cell population that coexpressed the chemokine receptor CCR6 and the skin-homing receptors CCR4 and CCR10. These cells were distinct from both T(H)-17 cells and T(H)1 cells. Downregulation of either the aryl hydrocarbon receptor (AHR) or the transcription factor RORC by RNA-mediated interference affected IL-22 production, whereas IL-17 production was affected only by downregulation of RORC by RNA-mediated interference. AHR agonists substantially altered the balance of IL-22- versus IL-17-producing cells. This subset of IL-22-producing cells may be important in skin homeostasis and pathology.
Trifari
Sara
S
Department of Immunology, Genentech, South San Francisco, California, USA.
Kaplan
Charles D
CD
Tran
Elise H
EH
Crellin
Natasha K
NK
Spits
Hergen
H
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D015536:Down-Regulation; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000502:physiology; D054447:Receptors, CCR10 / Q000096:biosynthesis; D054398:Receptors, CCR4 / Q000096:biosynthesis; D054399:Receptors, CCR6 / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000097043:Interleukin-22
D007371:Interferon-gamma; D018793:Interleukin-13; D020381:Interleukin-17; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D054399:Receptors, CCR6; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D000097043:Interleukin-22; C515706:CCR10 protein, human; C515354:CCR4 protein, human; C106311:CCR6 protein, human; C539900:RORC protein, human