Niedermeier, Marianne and Reich, Barbara and Gomez, Manuel Rodriguez and Denzel, Andrea and Schmidbauer, Kathrin and Goebel, Nicole and Talke, Yvonne and Schweda, Frank and Mack, Matthias (2009) CD4(+) T cells control the differentiation of Gr1(+) monocytes into fibrocytes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106 (42). pp. 17892-17897. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
Fibrocytes are collagen-type-I-producing cells that arise at low frequency from hematopoietic cells. We have analyzed in mice which leukocyte subsets are required for generation of fibrocytes and show that murine fibrocytes develop from the subpopulation of CD11b(+) CD115(+) Gr1(+) monocytes under the control of CD4(+) T cells. In the absence of CD4(+) T cells, differentiation of fibrocytes was markedly reduced in vitro and in vivo. In the presence of CD4(+) T cells, the characteristics of T-cell activation critically determined development of fibrocytes. Polyclonal activation of CD4(+) T cells induced the release of soluble factors that completely prevented the outgrowth of fibrocytes and could be identified as IL-2, TNF, IFN-gamma, and IL-4. Application of IL-2 and TNF significantly reduced the appearance of fibrocytes and the severity of fibrosis in the model of unilateral ureteral obstruction. In contrast, activation of CD4(+) T cells in the presence of calcineurin inhibitors, but not mTOR inhibitors, markedly enhanced the outgrowth of fibrocytes and renal deposition of collagen I. Taken together, we show that differentiation of fibrocytes is critically dependent on CD4(+) T cells and that the context of T-cell activation determines whether development of fibrocytes is supported or blocked. Our data may have implications for prevention of organ fibrosis in autoimmune diseases and transplantation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PERIPHERAL-BLOOD FIBROCYTES; NEPHROGENIC SYSTEMIC FIBROSIS; CIRCULATING FIBROCYTES; RENAL FIBROSIS; OBSTRUCTIVE NEPHROPATHY; MESENCHYMAL TRANSITION; HEPATIC-FIBROSIS; COLLAGEN; CYCLOSPORINE; CYTOKINES; fibrosis; transplantation; kidney; cytokines |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Sep 2020 06:56 |
| Last Modified: | 03 Sep 2020 06:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28262 |
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