Sphingosine 1-phosphate receptor 5 (S1PR5) regulates the peripheral retention of tissue-resident lymphocytes

Maximilien Evrard; Erica Wynne-Jones; Changwei Peng; Yu Kato; Susan N. Christo; Raissa Fonseca; Simone L. Park; Thomas N. Burn; Maleika Osman; Sapna Devi; Jerold Chun; Scott N. Mueller; George Kannourakis; Stuart P. Berzins; Daniel G. Pellicci; William R. Heath; Stephen C. Jameson; Laura K. Mackay

doi:10.1084/jem.20210116

Sphingosine 1-phosphate receptor 5 (S1PR5) regulates the peripheral retention of tissue-resident lymphocytes

Maximilien Evrard, Erica Wynne-Jones, Changwei Peng, Yu Kato, Susan N. Christo, Raissa Fonseca, Simone L. Park, Thomas N. Burn, Maleika Osman, Sapna Devi, Jerold Chun, Scott N. Mueller, George Kannourakis, Stuart P. Berzins, Daniel G. Pellicci, William R. Heath, Stephen C. Jameson, Laura K. Mackay

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Tissue-resident memory T (TRM) cells provide long-lasting immune protection. One of the key events controlling TRM cell development is the local retention of TRM cell precursors coupled to downregulation of molecules necessary for tissue exit. Sphingosine-1-phosphate receptor 5 (S1PR5) is a migratory receptor with an uncharted function in T cells. Here, we show that S1PR5 plays a critical role in T cell infiltration and emigration from peripheral organs, as well as being specifically downregulated in TRM cells. Consequentially, TRM cell development was selectively impaired upon ectopic expression of S1pr5, whereas loss of S1pr5 enhanced skin TRM cell formation by promoting peripheral T cell sequestration. Importantly, we found that T-bet and ZEB2 were required for S1pr5 induction and that local TGF-β signaling was necessary to promote coordinated Tbx21, Zeb2, and S1pr5 downregulation. Moreover, S1PR5-mediated control of tissue residency was conserved across innate and adaptive immune compartments. Together, these results identify the T-bet-ZEB2-S1PR5 axis as a previously unappreciated mechanism modulating the generation of tissue-resident lymphocytes.

Original language	English (US)
Article number	e20210116
Journal	Journal of Experimental Medicine
Volume	219
Issue number	1
DOIs	https://doi.org/10.1084/jem.20210116
State	Published - Oct 22 2021

Bibliographical note

Funding Information:
This work was supported by a Howard Hughes Medical Institute and Bill and Melinda Gates Foundation International Research Scholarship OPP1175796 to L.K. Mackay and Australian Research Council grant DP200102753 to L.K. Mackay and M. Evrard. M. Evrard is supported by the University of Melbourne McKenzie Postdoctoral Fellowship. S.L. Park is supported by a National Health and Medical Research Council Emerging Leadership Investigator grant. D.G. Pellicci is supported by a Commonwealth Serum Laboratories Centenary Fellowship. L.K. Mackay is a senior medical research fellow supported by the Sylvia and Charles Viertel Charitable Foundation.

Publisher Copyright:
© 2021 Evrard et al.

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10.1084/jem.20210116

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Evrard, M., Wynne-Jones, E., Peng, C., Kato, Y., Christo, S. N., Fonseca, R., Park, S. L., Burn, T. N., Osman, M., Devi, S., Chun, J., Mueller, S. N., Kannourakis, G., Berzins, S. P., Pellicci, D. G., Heath, W. R., Jameson, S. C., & Mackay, L. K. (2021). Sphingosine 1-phosphate receptor 5 (S1PR5) regulates the peripheral retention of tissue-resident lymphocytes. Journal of Experimental Medicine, 219(1), [e20210116]. https://doi.org/10.1084/jem.20210116

Evrard, M, Wynne-Jones, E, Peng, C, Kato, Y, Christo, SN, Fonseca, R, Park, SL, Burn, TN, Osman, M, Devi, S, Chun, J, Mueller, SN, Kannourakis, G, Berzins, SP, Pellicci, DG, Heath, WR, Jameson, SC & Mackay, LK 2021, 'Sphingosine 1-phosphate receptor 5 (S1PR5) regulates the peripheral retention of tissue-resident lymphocytes', Journal of Experimental Medicine, vol. 219, no. 1, e20210116. https://doi.org/10.1084/jem.20210116

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title = "Sphingosine 1-phosphate receptor 5 (S1PR5) regulates the peripheral retention of tissue-resident lymphocytes",

abstract = "Tissue-resident memory T (TRM) cells provide long-lasting immune protection. One of the key events controlling TRM cell development is the local retention of TRM cell precursors coupled to downregulation of molecules necessary for tissue exit. Sphingosine-1-phosphate receptor 5 (S1PR5) is a migratory receptor with an uncharted function in T cells. Here, we show that S1PR5 plays a critical role in T cell infiltration and emigration from peripheral organs, as well as being specifically downregulated in TRM cells. Consequentially, TRM cell development was selectively impaired upon ectopic expression of S1pr5, whereas loss of S1pr5 enhanced skin TRM cell formation by promoting peripheral T cell sequestration. Importantly, we found that T-bet and ZEB2 were required for S1pr5 induction and that local TGF-β signaling was necessary to promote coordinated Tbx21, Zeb2, and S1pr5 downregulation. Moreover, S1PR5-mediated control of tissue residency was conserved across innate and adaptive immune compartments. Together, these results identify the T-bet-ZEB2-S1PR5 axis as a previously unappreciated mechanism modulating the generation of tissue-resident lymphocytes. ",

author = "Maximilien Evrard and Erica Wynne-Jones and Changwei Peng and Yu Kato and Christo, {Susan N.} and Raissa Fonseca and Park, {Simone L.} and Burn, {Thomas N.} and Maleika Osman and Sapna Devi and Jerold Chun and Mueller, {Scott N.} and George Kannourakis and Berzins, {Stuart P.} and Pellicci, {Daniel G.} and Heath, {William R.} and Jameson, {Stephen C.} and Mackay, {Laura K.}",

note = "Funding Information: This work was supported by a Howard Hughes Medical Institute and Bill and Melinda Gates Foundation International Research Scholarship OPP1175796 to L.K. Mackay and Australian Research Council grant DP200102753 to L.K. Mackay and M. Evrard. M. Evrard is supported by the University of Melbourne McKenzie Postdoctoral Fellowship. S.L. Park is supported by a National Health and Medical Research Council Emerging Leadership Investigator grant. D.G. Pellicci is supported by a Commonwealth Serum Laboratories Centenary Fellowship. L.K. Mackay is a senior medical research fellow supported by the Sylvia and Charles Viertel Charitable Foundation. Publisher Copyright: {\textcopyright} 2021 Evrard et al.",

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AU - Evrard, Maximilien

AU - Wynne-Jones, Erica

AU - Peng, Changwei

AU - Kato, Yu

AU - Christo, Susan N.

AU - Fonseca, Raissa

AU - Park, Simone L.

AU - Burn, Thomas N.

AU - Osman, Maleika

AU - Devi, Sapna

AU - Chun, Jerold

AU - Mueller, Scott N.

AU - Kannourakis, George

AU - Berzins, Stuart P.

AU - Pellicci, Daniel G.

AU - Heath, William R.

AU - Jameson, Stephen C.

AU - Mackay, Laura K.

N1 - Funding Information: This work was supported by a Howard Hughes Medical Institute and Bill and Melinda Gates Foundation International Research Scholarship OPP1175796 to L.K. Mackay and Australian Research Council grant DP200102753 to L.K. Mackay and M. Evrard. M. Evrard is supported by the University of Melbourne McKenzie Postdoctoral Fellowship. S.L. Park is supported by a National Health and Medical Research Council Emerging Leadership Investigator grant. D.G. Pellicci is supported by a Commonwealth Serum Laboratories Centenary Fellowship. L.K. Mackay is a senior medical research fellow supported by the Sylvia and Charles Viertel Charitable Foundation. Publisher Copyright: © 2021 Evrard et al.

PY - 2021/10/22

Y1 - 2021/10/22

N2 - Tissue-resident memory T (TRM) cells provide long-lasting immune protection. One of the key events controlling TRM cell development is the local retention of TRM cell precursors coupled to downregulation of molecules necessary for tissue exit. Sphingosine-1-phosphate receptor 5 (S1PR5) is a migratory receptor with an uncharted function in T cells. Here, we show that S1PR5 plays a critical role in T cell infiltration and emigration from peripheral organs, as well as being specifically downregulated in TRM cells. Consequentially, TRM cell development was selectively impaired upon ectopic expression of S1pr5, whereas loss of S1pr5 enhanced skin TRM cell formation by promoting peripheral T cell sequestration. Importantly, we found that T-bet and ZEB2 were required for S1pr5 induction and that local TGF-β signaling was necessary to promote coordinated Tbx21, Zeb2, and S1pr5 downregulation. Moreover, S1PR5-mediated control of tissue residency was conserved across innate and adaptive immune compartments. Together, these results identify the T-bet-ZEB2-S1PR5 axis as a previously unappreciated mechanism modulating the generation of tissue-resident lymphocytes.

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Sphingosine 1-phosphate receptor 5 (S1PR5) regulates the peripheral retention of tissue-resident lymphocytes

Abstract

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