The Protein Phosphatase Shp1 Regulates Invariant NKT Cell Effector Differentiation Independently of TCR and Slam Signaling

The Journal of Immunology : Official Journal of the American Association of Immunologists
Mayra Cruz TleugabulovaThierry Mallevaey

Abstract

Invariant NKT (iNKT) cells are innate lipid-reactive T cells that develop and differentiate in the thymus into iNKT1/2/17 subsets, akin to TH1/2/17 conventional CD4 T cell subsets. The factors driving the central priming of iNKT cells remain obscure, although strong/prolonged TCR signals appear to favor iNKT2 cell development. The Src homology 2 domain-containing phosphatase 1 (Shp1) is a protein tyrosine phosphatase that has been identified as a negative regulator of TCR signaling. In this study, we found that mice with a T cell-specific deletion of Shp1 had normal iNKT cell numbers and peripheral distribution. However, iNKT cell differentiation was biased toward the iNKT2/17 subsets in the thymus but not in peripheral tissues. Shp1-deficient iNKT cells were also functionally biased toward the production of TH2 cytokines, such as IL-4 and IL-13. Surprisingly, we found no evidence that Shp1 regulates the TCR and Slamf6 signaling cascades, which have been suggested to promote iNKT2 differentiation. Rather, Shp1 dampened iNKT cell proliferation in response to IL-2, IL-7, and IL-15 but not following TCR engagement. Our findings suggest that Shp1 controls iNKT cell effector differentiation independently of positive selection throug...Continue Reading

References

Dec 1, 1995·The Journal of Experimental Medicine·A Bendelac
Dec 22, 1998·The Journal of Experimental Medicine·H S AzzamP E Love
Sep 24, 2002·Nature Immunology·Jennifer L MatsudaMitchell Kronenberg
Feb 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Thomas RansonJames P Di Santo
Apr 12, 2003·The Journal of Experimental Medicine·Taehoon ChunChyung-Ru Wang
Feb 16, 2005·Nature Medicine·Kim E NicholsPaul L Stein
Feb 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jens SchümannH Robson MacDonald
Dec 16, 2006·Blood·Hiroyuki KishimotoAkira Suzuki
Sep 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ben A CrokerBruce Alan Beutler
Nov 19, 2008·The Journal of Experimental Medicine·Asuka TerashimaMasaru Taniguchi
Mar 7, 2009·European Journal of Immunology·Elvire BourgeoisAndré Herbelin
Mar 18, 2009·Immunological Reviews·Ulrike Lorenz
Jul 6, 2010·Nature Immunology·Michael A WeinreichKristin A Hogquist
Aug 11, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carla C FowlerPhilip D Greenberg
Dec 2, 2010·International Immunology·Tomonori IyodaKayo Inaba
May 25, 2011·The Journal of Experimental Medicine·Amy E MoranKristin A Hogquist
Dec 14, 2011·Annual Review of Immunology·Gretta L StriteskyKristin A Hogquist
Jan 10, 2012·Annual Review of Immunology·Steven Z JosefowiczAlexander Y Rudensky
Jan 22, 2013·Nature Reviews. Immunology·Patrick J BrennanMichael B Brenner
Jan 29, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mala DuttaPamela L Schwartzberg
Feb 22, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna NapolitanoGiulia Casorati
Apr 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Natalia ZiętaraAndreas Krueger
Jun 26, 2013·The Journal of Experimental Medicine·Dylan J JohnsonBenjamin G Neel
Oct 15, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Taishan HuJose Alberola-Ila
Nov 19, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mihalis VerykokakisBarbara L Kee
Dec 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Romain BedelLaurent Gapin
Jan 29, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Louise M D'CruzAnanda W Goldrath
Jul 6, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jennifer E CowanGraham Anderson

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Citations

Mar 10, 2020·F1000Research·Kristin Hogquist, Hristo Georgiev
Nov 17, 2020·Frontiers in Immunology·Georgia PapadogianniHristo Georgiev
Dec 23, 2020·Molecular Immunology·Marion SalouOlivier Lantz

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