The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Immune homeostasis enforced by co-localized effector and regulatory T cells
Open accessAbstract
FOXP3+ regulatory T cells (Treg cells) prevent autoimmunity by limiting the effector activity of T cells that have escaped thymic negative selection or peripheral inactivation. Despite the information available about molecular factors mediating the suppressive function of Treg cells, the relevant cellular events in intact tissues remain largely unexplored, and whether Treg cells prevent activation of self-specific T cells or primarily limit damage from such cells has not been determined. Here we use multiplex, quantitative imaging in mice to show that, within secondary lymphoid tissues, highly suppressive Treg cells expressing phosphorylated STAT5 exist in discrete clusters with rare IL-2-positive T cells that are activated by self-antigens. This local IL-2 induction of STAT5 phosphorylation in Treg cells is part of a feedback circuit that limits further autoimmune responses. Inducible ablation of T cell receptor expression by Treg cells reduces their regulatory capacity and disrupts their localization in clusters, resulting in uncontrolled effector T cell responses. Our data thus reveal that autoreactive T cells are activated to cytokine production on a regular basis, with physically co-clustering T cell receptor-stimulated Treg cells responding in a negative feedback manner to suppress incipient autoimmunity and maintain immune homeostasis.
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Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992
Vignali, D. A. A., Collison, L. W., & Workman, C. J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2343 · Cited by 3,463
CTLA-4 Control over Foxp3 + Regulatory T Cell Function
Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., & Sakaguchi, S. (2008) · Science · doi:10.1126/science.1160062 · Cited by 2,956
Regulatory T cells: mechanisms of differentiation and function
Josefowicz, S. Z., Lu, L.-F., & Rudensky, A. Y. (2012) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141623 · Cited by 2,866
Self-citationDeaglio, S., Dwyer, K. M., Gao, W., Friedman, D., Usheva, A., Erat, A., Chen, J.-F., Enjyoji, K., Linden, J., Oukka, M., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062512 · Cited by 2,470
A function for interleukin 2 in Foxp3-expressing regulatory T cells
Fontenot, J. D., Rasmussen, J. P., Gavin, M. A., & Rudensky, A. Y. (2005) · Nature Immunology · doi:10.1038/ni1263 · Cited by 1,819
Self-citationMechanisms of Foxp3+ T Regulatory Cell-Mediated Suppression
Shevach, E. M. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.010 · Cited by 1,754
T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases
Mempel, T. R., Henrickson, S. E., & von Andrian, U. H. (2004) · Nature · doi:10.1038/nature02238 · Cited by 1,714
Pandiyan, P., Zheng, L., Ishihara, S., Reed, J., & Lenardo, M. J. (2007) · Nature Immunology · doi:10.1038/ni1536 · Cited by 1,286
Setoguchi, R., Hori, S., Takahashi, T., & Sakaguchi, S. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041982 · Cited by 1,235
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Regulatory T cells in cancer immunotherapy
Tanaka, A., & Sakaguchi, S. (2017) · Cell Research · doi:10.1038/cr.2016.151 · Cited by 1,860
T follicular helper cell biology: a decade of discovery and diseases
Crotty, S. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.011 · Cited by 1,591
Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma
Ji, A. L., Rubin, A. J., Thrane, K., Jiang, S., Reynolds, D. L., Meyers, R. M., Guo, M. G., George, B. M., Mollbrink, A., Bergenstråhle, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.039 · Cited by 1,117
“Treg and effector cell proximity in secondary lymphoid organs influences immunosuppressive function (Liu et al., 2015), and, similarly, we observed co-localization between Tregs and CD8 T cells in 5/12 FOVs with sufficient numbers of cells for systematic analysis of distance between Tregs and CD8 T cells (Figures 5F–5…”
BackgroundRegulatory T Cells and Human Disease
Sakaguchi, S., Mikami, N., Wing, J. B., Tanaka, A., Ichiyama, K., & Ohkura, N. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041717 · Cited by 1,120
IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance
Munn, D. H., & Mellor, A. L. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.01.002 · Cited by 1,041
Metadata
- Authors
- Liu, Z., Gerner, M. Y., Van Panhuys, N., Levine, A. G., Rudensky, A. Y., & Germain, R. N.
- Venue
- Nature
- Published
- 2015-11-25
- Volume
- 528
- Issue
- 7581
- Pages
- 225-230
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2177188076
- Cited by
- 317
- References
- 37
- FWCI
- 16.63
- Type
- journal article
- Language
- en
- Open access
- green
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- Liu, Z., Gerner, M. Y., Van Panhuys, N., Levine, A. G., Rudensky, A. Y., & Germain, R. N. (2015). Immune homeostasis enforced by co-localized effector and regulatory T cells. Nature. https://doi.org/10.1038/nature16169
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