TY  - JOUR
A1  - Muhammad, Khalid
A1  - Rudolf, Ronald
A1  - Pham, Duong Anh Thuy
A1  - Klein-Hessling, Stefan
A1  - Takata, Katsuyoshi
A1  - Matsushita, Nobuko
A1  - Ellenrieder, Volker
A1  - Kondo, Eisaku
A1  -  Serfling, Edgar
T1  - Induction of Short NFATc1/αA Isoform Interferes with Peripheral B Cell Differentiation
JF  - Frontiers in Immunology
N2  - In lymphocytes, immune receptor signals induce the rapid nuclear translocation of preformed cytosolic NFAT proteins. Along with co-stimulatory signals, persistent immune receptor signals lead to high levels of NFATc1/αA, a short NFATc1 isoform, in effector lymphocytes. Whereas NFATc1 is not expressed in plasma cells, in germinal centers numerous centrocytic B cells express nuclear NFATc1/αA. When overexpressed in chicken DT40 B cells or murine WEHI 231 B cells, NFATc1/αA suppressed their cell death induced by B cell receptor signals and affected the expression of genes controlling the germinal center reaction and plasma cell formation. Among those is the Prdm1 gene encoding Blimp-1, a key factor of plasma cell formation. By binding to a regulatory DNA element within exon 1 of the Prdm1 gene, NFATc1/αA suppresses Blimp-1 expression. Since expression of a constitutive active version of NFATc1/αA interfered with Prdm1 RNA expression, LPS-mediated differentiation of splenic B cells to plasmablasts in vitro and reduced immunoglobulin production in vivo, one may conclude that NFATc1/αA plays an important role in controlling plasmablast/plasma cell formation.
KW  - B cells
KW  - DT40 cells
KW  - germinal center
KW  - NFATc1
KW  - plasmablasts
KW  - plasma cells
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197501
SN  - 1664-3224
VL  - 9
IS  - 32
ER  - 
TY  - JOUR
A1  - Alrefai, Hani
A1  - Muhammad, Khalid
A1  - Rudolf, Ronald
A1  - Pham, Duong Anh Thuy
A1  - Klein-Hessling, Stefan
A1  - Patra, Amiya K.
A1  - Avots, Andris
A1  - Bukur, Valesca
A1  - Sahin,, Ugur
A1  - Tenzer, Stefan
A1  - Goebeler, Matthias
A1  - Kerstan, Andreas
A1  - Serfling, Edgar
T1  - NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells
JF  - Nature Communications
N2  - Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.
KW  - B cells
KW  - psoriasis
KW  - interleukins
KW  - inflammation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173053
VL  - 7
ER  -