Loss of Phosphatase and Tensin Homolog in APCs Impedes Th17-Mediated Autoimmune Encephalomyelitis

Sahin E, Brunner JS, Kral JB, Kuttke M, Hanzl L, Datler H, Paar H, Neuwinger N, Saferding V, Zinser E, Halfmann A, Soukup K, Hainzl E, Lohmeyer T, Niederreiter B, Haider T, Dohnal AM, Krönke G, Blüml S, Schabbauer G (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Journal of Immunology American Association of Immunologists

Publisher: American Association of Immunologists

Book Volume: 195

Pages Range: 2560-70

Journal Issue: 6

DOI: 10.4049/jimmunol.1402511

Abstract

The PI3K signaling cascade in APCs has been recognized as an essential pathway to initiate, maintain, and resolve immune responses. In this study, we demonstrate that a cell type-specific loss of the PI3K antagonist phosphatase and tensin homolog (PTEN) in myeloid cells renders APCs toward a regulatory phenotype. APCs deficient for PTEN exhibit reduced activation of p38 MAPK and reduced expression of T cell-polarizing cytokines. Furthermore, PTEN deficiency leads to upregulation of markers for alternative activation, such as Arginase 1, with concomitant downregulation of inducible NO synthase in APCs in vitro and in vivo. As a result, T cell polarization was dysfunctional in PTEN(-/-) APCs, in particular affecting the Th17 cell subset. Intriguingly, mice with cell type-specific deletions of PTEN-targeting APCs were protected from experimental autoimmune encephalomyelitis, which was accompanied by a pronounced reduction of IL-17- and IL-22-producing autoreactive T cells and reduced CNS influx of classically activated monocytes/macrophages. These observations support the notion that activation of the PI3K signaling cascade promotes regulatory APC properties and suppresses pathogenic T cell polarization, thereby reducing the clinical symptoms and pathology of experimental autoimmune encephalomyelitis.

Authors with CRIS profile

Gerhard Krönke Professur für Translationale Immunologie

Involved external institutions

Medizinische Universität Wien AT Austria (AT) St. Anna Kinderkrebsforschung AT Austria (AT)

How to cite

APA:

Sahin, E., Brunner, J.S., Kral, J.B., Kuttke, M., Hanzl, L., Datler, H.,... Schabbauer, G. (2015). Loss of Phosphatase and Tensin Homolog in APCs Impedes Th17-Mediated Autoimmune Encephalomyelitis. Journal of Immunology, 195(6), 2560-70. https://doi.org/10.4049/jimmunol.1402511

MLA:

Sahin, Emine, et al. "Loss of Phosphatase and Tensin Homolog in APCs Impedes Th17-Mediated Autoimmune Encephalomyelitis." Journal of Immunology 195.6 (2015): 2560-70.

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