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TGF-β Promotes the Postselection Thymic Development and Peripheral Function of IFN-γ-Producing Invariant NKT cells

Morgan, Roxroy C. ; Frank, Cameron ; Greger, Munmun ; Attaway, Mary ; Sigvardsson, Mikael LU ; Bartom, Elizabeth T. and Kee, Barbara L. (2023) In Journal of Immunology 211(9). p.1376-1384
Abstract

IFN-γproducing invariant NKT (iNKT)1 cells are lipid-reactive innate-like lymphocytes that are resident in the thymus and peripheral tissues where they protect against pathogenic infection. The thymic functions of iNKT1 cells are not fully elucidated, but subsets of thymic iNKT cells modulate CD8 T cell, dendritic cell, B cell, and thymic epithelial cell numbers or function. In this study, we show that a subset of murine thymic iNKT1 cells required TGF-βinduced signals for their postselection development, to maintain hallmark TGF-βinduced genes, and for expression of the adhesion receptors CD49a and CD103. However, the residency-associated receptor CD69 was not TGFβ signalinγdependent. Recently described CD244+ c2 thymic iNKT1 cells,... (More)

IFN-γproducing invariant NKT (iNKT)1 cells are lipid-reactive innate-like lymphocytes that are resident in the thymus and peripheral tissues where they protect against pathogenic infection. The thymic functions of iNKT1 cells are not fully elucidated, but subsets of thymic iNKT cells modulate CD8 T cell, dendritic cell, B cell, and thymic epithelial cell numbers or function. In this study, we show that a subset of murine thymic iNKT1 cells required TGF-βinduced signals for their postselection development, to maintain hallmark TGF-βinduced genes, and for expression of the adhesion receptors CD49a and CD103. However, the residency-associated receptor CD69 was not TGFβ signalinγdependent. Recently described CD244+ c2 thymic iNKT1 cells, which produce IFNγ without exogenous stimulation and have NK-like characteristics, reside in this TGF-βresponsive population. Liver and spleen iNKT1 cells do not share this TGFβ gene signature, but nonetheless TGFβ impacts liver iNKT1 cell phenotype and function. Our findings provide insight into the heterogeneity of mechanisms guiding iNKT1 cell development in different tissues and suggest a close association between a subset of iNKT1 cells and TGF-βproducing cells in the thymus that support their development. The Journal of Immunology, 2023, 211: 1376-1384.

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Contribution to journal
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published
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in
Journal of Immunology
volume
211
issue
9
pages
9 pages
publisher
American Association of Immunologists
external identifiers
  • pmid:37702745
  • scopus:85176546289
ISSN
0022-1767
DOI
10.4049/jimmunol.2200809
language
English
LU publication?
yes
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Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases Grant AI123395 (to B.L.K.), National Cancer Institute Grant P30 CA014599 (to The University of Chicago Comprehensive Cancer Center), and by National Institute of Allergy and Infectious Diseases Grants T32 HD007009 (to R.C.M.) and T32 AI007090 (to M.A.). Publisher Copyright: © 2023 by TheAmericanAssociation of Immunologists, Inc.
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e8e171f6-c6b1-4b7e-b2ee-2e519a766c99
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2024-01-03 12:27:23
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2024-04-18 09:52:52
@article{e8e171f6-c6b1-4b7e-b2ee-2e519a766c99,
  abstract     = {{<p>IFN-γproducing invariant NKT (iNKT)1 cells are lipid-reactive innate-like lymphocytes that are resident in the thymus and peripheral tissues where they protect against pathogenic infection. The thymic functions of iNKT1 cells are not fully elucidated, but subsets of thymic iNKT cells modulate CD8 T cell, dendritic cell, B cell, and thymic epithelial cell numbers or function. In this study, we show that a subset of murine thymic iNKT1 cells required TGF-βinduced signals for their postselection development, to maintain hallmark TGF-βinduced genes, and for expression of the adhesion receptors CD49a and CD103. However, the residency-associated receptor CD69 was not TGFβ signalinγdependent. Recently described CD244+ c2 thymic iNKT1 cells, which produce IFNγ without exogenous stimulation and have NK-like characteristics, reside in this TGF-βresponsive population. Liver and spleen iNKT1 cells do not share this TGFβ gene signature, but nonetheless TGFβ impacts liver iNKT1 cell phenotype and function. Our findings provide insight into the heterogeneity of mechanisms guiding iNKT1 cell development in different tissues and suggest a close association between a subset of iNKT1 cells and TGF-βproducing cells in the thymus that support their development. The Journal of Immunology, 2023, 211: 1376-1384.</p>}},
  author       = {{Morgan, Roxroy C. and Frank, Cameron and Greger, Munmun and Attaway, Mary and Sigvardsson, Mikael and Bartom, Elizabeth T. and Kee, Barbara L.}},
  issn         = {{0022-1767}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{9}},
  pages        = {{1376--1384}},
  publisher    = {{American Association of Immunologists}},
  series       = {{Journal of Immunology}},
  title        = {{TGF-β Promotes the Postselection Thymic Development and Peripheral Function of IFN-γ-Producing Invariant NKT cells}},
  url          = {{http://dx.doi.org/10.4049/jimmunol.2200809}},
  doi          = {{10.4049/jimmunol.2200809}},
  volume       = {{211}},
  year         = {{2023}},
}