Integration of T-cell receptor, Notch and cytokine signals programs mouse γδ T-cell effector differentiation

Immunology and Cell Biology
Payam ZarinJuan Carlos Zúñiga-Pflücker

Abstract

γδ T-cells perform a wide range of tissue- and disease-specific functions that are dependent on the effector cytokines produced by these cells. However, the aggregate signals required for the development of interferon-γ (IFNγ) and interleukin-17 (IL-17) producing γδ T-cells remain unknown. Here, we define the cues involved in the functional programming of γδ T-cells, by examining the roles of T-cell receptor (TCR), Notch, and cytokine-receptor signaling. KN6 γδTCR-transduced Rag2-/- T-cell progenitors were cultured on stromal cells variably expressing TCR and Notch ligands, supplemented with different cytokines. We found that distinct combinations of these signals are required to program IFNγ versus IL-17 producing γδ T-cell subsets, with Notch and weak TCR ligands optimally enabling development of γδ17 cells in the presence of IL-1β, IL-21 and IL-23. Notably, these cytokines were also shown to be required for the intrathymic development of γδ17 cells. Together, this work provides a framework of how signals downstream of TCR, Notch and cytokine receptors integrate to program the effector function of IFNγ and IL-17 producing γδ T-cell subsets.

References

Jul 1, 1990·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·R FelixH Fleisch
Dec 14, 2002·Immunity·Thomas M Schmitt, Juan Carlos Zúñiga-Pflücker
Apr 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria CiofaniJuan Carlos Zúñiga-Pflücker
Jan 20, 2005·The Journal of Experimental Medicine·Claire L LangrishDaniel J Cua
Apr 12, 2005·Science·Erin J AdamsK Christopher Garcia
May 28, 2008·The Journal of Experimental Medicine·Matthias LochnerGérard Eberl
Sep 19, 2008·Nature Immunology·Tracy S P HengUNKNOWN Immunological Genome Project Consortium
Jun 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sumanta MukherjeeNicholas W Lukacs
Oct 16, 2009·European Journal of Immunology·Jan D HaasImmo Prinz
Jan 12, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeong-su DoBooki Min
Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Shamsul AlamKoji Yasutomo
Jun 12, 2010·Nature Reviews. Immunology·Marc BonnevilleWilli K Born
Jun 16, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mahmood MohtashamiJuan Carlos Zúñiga-Pflücker
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Susannah D BarbeeAdrian C Hayday
Apr 8, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen J LalorKingston H G Mills
Sep 6, 2012·European Journal of Immunology·Caroline E SuttonKingston H G Mills
Dec 26, 2012·Trends in Immunology·Yueh-hsiu ChienImmo Prinz
Mar 5, 2013·Advances in Experimental Medicine and Biology·Julie C Ribot, Bruno Silva-Santos
Apr 27, 2013·International Reviews of Immunology·Leonardo M R Ferreira
Aug 10, 2013·European Journal of Immunology·Immo PrinzDaniel J Pennington
Aug 31, 2013·International Immunology·Mahmood MohtashamiJuan Carlos Zúñiga-Pflücker
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Payam ZarinJuan Carlos Zúñiga-Pflücker
May 7, 2014·Nature Communications·Ada YesteFrancisco J Quintana
Nov 28, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Masataka NakamuraYasunobu Yoshikai
Feb 11, 2015·Cancer Research·Margarida ReiBruno Silva-Santos
Apr 14, 2015·Cellular Immunology·Payam ZarinJuan Carlos Zúñiga-Pflücker
Jun 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Francisco Ramírez-ValleJason G Cyster
Jul 1, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amélie LombesBruno Martin

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Citations

Sep 18, 2018·Immunology and Cell Biology·Gina J Fiala, Bruno Silva-Santos
Dec 16, 2018·Immunology·Nital SumariaDaniel J Pennington
Aug 28, 2020·Immunological Reviews·Mia Hamilton JeeCharlotte Menné Bonefeld
Nov 21, 2018·The Journal of Experimental Medicine·Inga SandrockImmo Prinz
Jul 10, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adrian C Hayday
Jan 30, 2019·Immunology and Cell Biology·Anne C La Flamme
Nov 17, 2020·Immunological Reviews·Gina J FialaBruno Silva-Santos
Oct 16, 2020·Immunological Reviews·Michele K Anderson, Johanna S Selvaratnam

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Methods Mentioned

BETA
ELISA
flow cytometry
flow
PMA
PCR

Software Mentioned

Flowjo
Prism

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