TY  - JOUR
A1  - Serfling, Edgar
A1  - Rudolf, Ronald
A1  - Busch, Rhoda
A1  - Patra, Amiya K.
A1  - Muhammad, Khalid
A1  - Avots, Andris
A1  - Andrau, Jean-Christophe
A1  - Klein-Hessling, Stefan
T1  - Architecture and expression of the Nfatc1 gene in lymphocytes
N2  - In lymphocytes, the three NFAT factors NFATc1 (also designated as NFAT2), NFATc2 (NFAT1), and NFATc3 (NFAT4 or NFATx) are expressed and are the targets of immune receptor signals, which lead to a rapid rise of intracellular Ca++, the activation of phosphatase calcineurin, and to the activation of cytosolic NFATc proteins. In addition to rapid activation of NFAT factors, immune receptor signals lead to accumulation of the short NFATc1/αA isoform in lymphocytes which controls their proliferation and survival. In this mini-review, we summarize our current knowledge on the structure and transcription of the Nfatc1 gene in lymphocytes, which is controlled by two promoters, two poly A addition sites and a remote downstream enhancer. The Nfatc1 gene resembles numerous primary response genes (PRGs) induced by LPS in macrophages. Similar to the PRG promoters, the Nfatc1 promoter region is organized in CpG islands, forms DNase I hypersensitive sites, and is marked by histone tail modifications before induction. By studying gene induction in lymphocytes in detail, it will be important to elucidate whether the properties of the Nfatc1 induction are not only typical for the Nfatc1 gene but also for other transcription factor genes expressed in lymphocytes.
KW  - transcription
KW  - chromatin
KW  - induction
KW  - lymphocytes
KW  - Nfatc1
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112718
ER  - 
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  -