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001-es BibID:BIBFORM043020
035-os BibID:PMID:23184643
Első szerző:Izsépi Emese
Cím:Membrane microdomain organization, calcium signal, and NFAT activation as an important axis in polarized Th cell function / Emese Izsepi, Leonora Himer, Orsolya Szilagyi, Peter Hajdu, György Panyi, Gloria Laszlo, Janos Matko
Dátum:2013
Megjegyzések:T helper lymphocytes become polarized upon antigen and cytokine stimuli received after their maturation in the thymus. Since the balance of Th1 and Th2 responses is critical in healthy and pathological immune responses, understanding the molecular base of T cell polarization still remained an important question. Using our Th0/Th1/Th2 hybridoma model system, we performed a comparative study on polarized Th1 and Th2 cells in terms of their membrane raft expression/composition, their TCR mediated activation signaling, and sensitivity to activation-induced cell death (AICD) using flow and image cytometric methods. We show here that the TCR stimulation induced more intense and sustained Ca(2+) -response in Th1 cells compared to Th2 ones correlates well with a shorter nuclear residence time of the Ca(2+) -dependent NFAT transcription factor in Th2 cells. In addition, NFAT translocation directly depended on lipid raft integrity/membrane cholesterol level. Expression pattern of raftophilic accessory proteins (CD4, CD59, and CD48) and lipids (GM1, cholesterol) were also different in the Th1 and Th2 hybridomas, similarly to differentiated spleen Th cells. The activation-induced, remarkably clustered and polarized membrane distribution of TCR/CD3 complex in Th1, but not in Th2 cells, together with an increased raft localization of Kv1.3 ion channels regulating the Ca(2+) -response, are consistent with the above properties of NFAT. Finally, the polarized Th cells, especially Th1, were more sensitive to AICD than their unpolarized Th0 precursor. These results suggest that the membrane microdomain organization-Ca(2+) -signaling-NFAT activation axis is an important determinant of polarized Th cell effector function and fate.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
ACTIVATION
article
Calcium
cell function
Cells
Cholesterol
Comparative Study
cytometry
EXPRESSION
FLOW
Hungary
immunology
Ion Channels
lipid raft
Lipids
lymphocyte
Lymphocytes
methods
Proteins
Spleen
Th1 Cells
Th2 Cells
time
Biophysics
cell biology
Research
Megjelenés:Cytometry. Part A. - 83 : 2 (2013), p. 185-196. -
További szerzők:Himer Leonóra Szilágyi Orsolya (1985-) (molekuláris biológus, biokémikus) Hajdu Péter (1975-) (biofizikus) Panyi György (1966-) (biofizikus) László Glória Matkó János (1952-) (biológus)
Pályázati támogatás:64696
OTKA
CK 80935
OTKA
TÁMOP-4.2.1./B-09/1/KMR-2010-0003
TÁMOP
Internet cím:DOI
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