| Author |
Buchtler S, Frühauf A, Neumayer S, Schmidbauer K, Talke Y, Winter-Köhler F, Balam S, Landgraf K, Gebhard C, Rehli M, Schlieckau FV, Beck M, Günther F, Fleck M, Renner K, Mack M.
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| Abstract |
Repetitive injuries are an important trigger of progressive fibrosis. To study if repetitive injuries induce an accelerated profibrotic process, also called "fibrosis-memory," we established an experimental system with two consecutive, clearly separated insults in a model of renal fibrosis with reversible and irreversible unilateral ureteral obstruction. We found that a preceding fibrotic event of one kidney markedly enhanced subsequent development of fibrosis in the contralateral kidney. Aggravation of fibrosis during the second insult was dependent on memory CD4+ T cells. T cell depletion abrogated the fibrosis-memory effect, while adoptive transfer of memory T cells from fibrotic mice enhanced fibrosis in the recipients. Moreover, IL-3 production by memory CD4+ T cells was essential for aggravation of fibrosis in memory situations. In patients with systemic sclerosis, IL-3 expression by T cells was markedly increased, especially after a long disease duration accompanied by involvement of internal organs. In summary, our data identify IL-3-mediated fibrosis-memory as an important driver of progressive fibrosis.
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