title: Effector γδ T Cell Differentiation Relies on Master but Not Auxiliary Th Cell Transcription Factors.
abstract: γδ T lymphocytes are programmed into distinct IFN-γ-producing CD27(+) (γδ27(+)) and IL-17-producing CD27(-) (γδ27(-)) subsets that play key roles in protective or pathogenic immune responses. Although the signature cytokines are shared with their αβ Th1 (for γδ27(+)) and Th17 (for γδ27(-)) cell counterparts, we dissect in this study similarities and differences in the transcriptional requirements of murine effector γδ27(+), γδ27(-)CCR6(-), and γδ27(-)CCR6(+) γδ T cell subsets and αβ T cells. We found they share dependence on the master transcription factors T-bet and RORγt for IFN-γ and IL-17 production, respectively. However, Eomes is fully dispensable for IFN-γ production by γδ T cells. Furthermore, the Th17 cell auxiliary transcription factors RORα and BATF are not required for IL-17 production by γδ27(-) cell subsets. We also show that γδ27(-) (but not γδ27(+)) cells become polyfunctional upon IL-1β plus IL-23 stimulation, cosecreting IL-17A, IL-17F, IL-22, GM-CSF, and IFN-γ. Collectively, our in vitro and in vivo data firmly establish the molecular segregation between γδ27(+) and γδ27(-) T cell subsets and provide novel insight on the nonoverlapping transcriptional networks that control the differentiation of effector γδ versus αβ T cell subsets.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal;
authors.forename: Joana
authors.identifier: 0000-0002-3370-4990
authors.initials: J
authors.lastname: Barros-Martins
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal;
authors.forename: Nina
authors.identifier: 0000-0002-4460-8195
authors.initials: N
authors.lastname: Schmolka
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal;
authors.forename: Diana
authors.initials: D
authors.lastname: Fontinha
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal;
authors.forename: Marta
authors.identifier: 0000-0003-3733-4963
authors.initials: M
authors.lastname: Pires de Miranda
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal;
authors.forename: J Pedro
authors.identifier: 0000-0001-6982-9253
authors.initials: JP
authors.lastname: Simas
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal;
authors.forename: Ingrid
authors.initials: I
authors.lastname: Brok
authors.affiliation: Laboratory for Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, United Kingdom; and.
authors.forename: Cristina
authors.identifier: 0000-0001-6746-932X
authors.initials: C
authors.lastname: Ferreira
authors.affiliation: Laboratory for Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, United Kingdom; and.
authors.forename: Marc
authors.identifier: 0000-0002-1478-9562
authors.initials: M
authors.lastname: Veldhoen
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; Instituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal karineserre@medicina.ulisboa.pt bssantos@medicina.ulisboa.pt.
authors.forename: Bruno
authors.initials: B
authors.lastname: Silva-Santos
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; karineserre@medicina.ulisboa.pt bssantos@medicina.ulisboa.pt.
authors.forename: Karine
authors.identifier: 0000-0001-9152-4739
authors.initials: K
authors.lastname: Serre
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000502:physiology; D058504:Th17 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000097043:Interleukin-22; D000098815:T-bet Transcription Factor
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000097043:Interleukin-22; D000098815:T-bet Transcription Factor; C431772:Batf protein, mouse; C539901:Rorc protein, mouse