Thymic self-reactivity selects natural interleukin 17-producing T cells that can regulate peripheral inflammation.
Interleukin 17 (IL-17)-producing CD4(+) helper T cells (T(H)-17 cells) share a developmental relationship with Foxp3(+) regulatory T cells (T(reg) cells). Here we show that a T(H)-17 population differentiates in the thymus in a manner influenced by recognition of self antigen and by the cytokines IL-6 and transforming growth factor-beta (TGF-beta). Like previously described T(H)-17 cells, the T(H)-17 cells that developed in the thymus expressed the transcription factor RORgamma t and the IL-23 receptor. These cells also expressed alpha(4)beta(1) integrins and the chemokine receptor CCR6 and were recruited to the lung, gut and liver. In the liver, these cells secreted IL-22 in response to self antigen and mediated host protection during inflammation. Thus, T(H)-17 cells, like T(reg) cells, can be selected by self antigens in the thymus.
Marks
Benjamin R
BR
Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
Nowyhed
Heba N
HN
Choi
Jin-Young
JY
Poholek
Amanda C
AC
Odegard
Jared M
JM
Flavell
Richard A
RA
Craft
Joe
J
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016133:Polymerase Chain Reaction; D054399:Receptors, CCR6 / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
D001324:Autoantigens; D039041:Integrin alpha4beta1; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D054399:Receptors, CCR6; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D016212:Transforming Growth Factor beta; D000097043:Interleukin-22; C498126:CCR6 protein, mouse; C539901:Rorc protein, mouse