TY  - JOUR
A1  - Rauschenberger, Tabea
A1  - Schmitt, Viola
A1  - Azeem, Muhammad
A1  - Klein-Hessling, Stefan
A1  - Murti, Krisna
A1  - Grän, Franziska
A1  - Goebeler, Matthias
A1  - Kerstan, Andreas
A1  - Klein, Matthias
A1  - Bopp, Tobias
A1  - Serfling, Edgar
A1  - Muhammad, Khalid
T1  - T cells control chemokine secretion by keratinocytes
JF  - Frontiers in Immunology
N2  - The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8\(^+\)T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8\(^+\)T cells. One key molecule is IFN-γ that is synthesized by CD8\(^+\)T cells under the control of NFATc1 and NFATc2. CD8\(^+\)T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. In addition, CD8\(^+\)T cells induced numerous type I IFN-inducible “defense genes” in keratinocytes encoding the PD1 and CD40 ligands, TNF-α and caspase-1. The enhanced expression of type I IFN-inducible genes resembles the gene expression pattern at the dermal/epidermal interface in lichen planus, an inflammatory T lymphocyte-driven skin disease, in which we detected the expression of CXCL10 in keratinocytes in close vicinity to the infiltration front of T cells. These data reflect the multifaceted interplay of lymphocytes with keratinocytes at the molecular level.
KW  - chemokine
KW  - keratinocytes
KW  - IFN
KW  - lichen planus
KW  - T cells
KW  - Nfatc1
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195695
SN  - 1664-3224
VL  - 10
IS  - 1917
ER  - 
TY  - JOUR
A1  - Jost, Priska
A1  - Klein, Franziska
A1  - Brand, Benjamin
A1  - Wahl, Vanessa
A1  - Wyatt, Amanda
A1  - Yildiz, Daniela
A1  - Boehm, Ulrich
A1  - Niemeyer, Barbara A.
A1  - Vaeth, Martin
A1  - Alansary, Dalia
T1  - Acute downregulation but not genetic ablation of murine MCU impairs suppressive capacity of regulatory CD4 T cells
JF  - International Journal of Molecular Sciences
N2  - By virtue of mitochondrial control of energy production, reactive oxygen species (ROS) generation, and maintenance of Ca\(^{2+}\) homeostasis, mitochondria play an essential role in modulating T cell function. The mitochondrial Ca\(^{2+}\) uniporter (MCU) is the pore-forming unit in the main protein complex mediating mitochondrial Ca\(^{2+}\) uptake. Recently, MCU has been shown to modulate Ca\(^{2+}\) signals at subcellular organellar interfaces, thus fine-tuning NFAT translocation and T cell activation. The mechanisms underlying this modulation and whether MCU has additional T cell subpopulation-specific effects remain elusive. However, mice with germline or tissue-specific ablation of Mcu did not show impaired T cell responses in vitro or in vivo, indicating that ‘chronic’ loss of MCU can be functionally compensated in lymphocytes. The current work aimed to specifically investigate whether and how MCU influences the suppressive potential of regulatory CD4 T cells (Treg). We show that, in contrast to genetic ablation, acute siRNA-mediated downregulation of Mcu in murine Tregs results in a significant reduction both in mitochondrial Ca\(^{2+}\) uptake and in the suppressive capacity of Tregs, while the ratios of Treg subpopulations and the expression of hallmark transcription factors were not affected. These findings suggest that permanent genetic inactivation of MCU may result in compensatory adaptive mechanisms, masking the effects on the suppressive capacity of Tregs.
KW  - mitochondrial calcium uniporter
KW  - regulatory T cells
KW  - suppressive capacity
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313621
SN  - 1422-0067
VL  - 24
IS  - 9
ER  -