Lymphotoxin expression in human and murine renal allografts
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Lymphotoxin expression in human and murine renal allografts. / Seeger, Harald; Lindenmeyer, Maja T; Cohen, Clemens D; Jaeckel, Carsten; Nelson, Peter J; Chen, Jin; Edenhofer, Ilka; Kozakowski, Nicolas; Regele, Heinz; Boehmig, Georg; Brandt, Simone; Wuethrich, Rudolf P; Heikenwalder, Mathias; Fehr, Thomas; Segerer, Stephan.
in: PLOS ONE, Jahrgang 13, Nr. 1, 2018, S. e0189396.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Lymphotoxin expression in human and murine renal allografts
AU - Seeger, Harald
AU - Lindenmeyer, Maja T
AU - Cohen, Clemens D
AU - Jaeckel, Carsten
AU - Nelson, Peter J
AU - Chen, Jin
AU - Edenhofer, Ilka
AU - Kozakowski, Nicolas
AU - Regele, Heinz
AU - Boehmig, Georg
AU - Brandt, Simone
AU - Wuethrich, Rudolf P
AU - Heikenwalder, Mathias
AU - Fehr, Thomas
AU - Segerer, Stephan
PY - 2018
Y1 - 2018
N2 - The kidney is the most frequently transplanted solid organ. Recruitment of inflammatory cells, ranging from diffuse to nodular accumulations with defined microarchitecture, is a hallmark of acute and chronic renal allograft injury. Lymphotoxins (LTs) mediate the communication of lymphocytes and stromal cells and play a pivotal role in chronic inflammation and formation of lymphoid tissue. The aim of this study was to assess the expression of members of the LT system in acute rejection (AR) and chronic renal allograft injury such as transplant glomerulopathy (TG) and interstitial fibrosis/tubular atrophy (IFTA). We investigated differentially regulated components in transcriptomes of human renal allograft biopsies. By microarray analysis, we found the upregulation of LTβ, LIGHT, HVEM and TNF receptors 1 and 2 in AR and IFTA in human renal allograft biopsies. In addition, there was clear evidence for the activation of the NFκB pathway, most likely a consequence of LTβ receptor stimulation. In human renal allograft biopsies with transplant glomerulopathy (TG) two distinct transcriptional patterns of LT activation were revealed. By quantitative RT-PCR robust upregulation of LTα, LTβ and LIGHT was shown in biopsies with borderline lesions and AR. Immunohistochemistry revealed expression of LTβ in tubular epithelial cells and inflammatory infiltrates in transplant biopsies with AR and IFTA. Finally, activation of LT signaling was reproduced in a murine model of renal transplantation with AR. In summary, our results indicate a potential role of the LT system in acute renal allograft rejection and chronic transplant injury. Activation of the LT system in allograft rejection in rodents indicates a species independent mechanism. The functional role of the LT system in acute renal allograft rejection and chronic injury remains to be determined.
AB - The kidney is the most frequently transplanted solid organ. Recruitment of inflammatory cells, ranging from diffuse to nodular accumulations with defined microarchitecture, is a hallmark of acute and chronic renal allograft injury. Lymphotoxins (LTs) mediate the communication of lymphocytes and stromal cells and play a pivotal role in chronic inflammation and formation of lymphoid tissue. The aim of this study was to assess the expression of members of the LT system in acute rejection (AR) and chronic renal allograft injury such as transplant glomerulopathy (TG) and interstitial fibrosis/tubular atrophy (IFTA). We investigated differentially regulated components in transcriptomes of human renal allograft biopsies. By microarray analysis, we found the upregulation of LTβ, LIGHT, HVEM and TNF receptors 1 and 2 in AR and IFTA in human renal allograft biopsies. In addition, there was clear evidence for the activation of the NFκB pathway, most likely a consequence of LTβ receptor stimulation. In human renal allograft biopsies with transplant glomerulopathy (TG) two distinct transcriptional patterns of LT activation were revealed. By quantitative RT-PCR robust upregulation of LTα, LTβ and LIGHT was shown in biopsies with borderline lesions and AR. Immunohistochemistry revealed expression of LTβ in tubular epithelial cells and inflammatory infiltrates in transplant biopsies with AR and IFTA. Finally, activation of LT signaling was reproduced in a murine model of renal transplantation with AR. In summary, our results indicate a potential role of the LT system in acute renal allograft rejection and chronic transplant injury. Activation of the LT system in allograft rejection in rodents indicates a species independent mechanism. The functional role of the LT system in acute renal allograft rejection and chronic injury remains to be determined.
KW - Animals
KW - Biopsy
KW - DNA, Complementary
KW - Graft Rejection
KW - Humans
KW - Kidney
KW - Kidney Glomerulus
KW - Kidney Transplantation
KW - Lymphotoxin-alpha
KW - Mice
KW - Oligonucleotide Array Sequence Analysis
KW - RNA, Messenger
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Transplantation, Homologous
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1371/journal.pone.0189396
DO - 10.1371/journal.pone.0189396
M3 - SCORING: Journal article
C2 - 29300739
VL - 13
SP - e0189396
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 1
ER -
