Kidney-derived stromal cells modulate dendritic and T cell responses

Yanfei Huang, Peter Johnston, Borui Zhang, Asif Zakari, Tayseer Chowdhry, Rachel Ruckdeschel Smith, Eduardo Marbán, Hamid Rabb, Karl L. Womer

Research output: Contribution to journalArticlepeer-review

Abstract

Multipotent mesenchymal stromal cells from the bone marrow ameliorate acute kidney injury through a mechanism other than transdifferentiation into renal tissue. Stromal cells exert immunoregulatory effects on dendritic and T cells, both of which are important in the pathophysiology of immune-mediated kidney injury. We hypothesized that similar cells with immunoregulatory function exist within the adult kidney. We isolated murine kidney-derived cells with morphologic features, growth properties, and an immu- nophenotype characteristic of mesenchymal stromal cells. These cells lacked lineage markers and could be differentiated into mesodermal cell lineages, including osteocytes and adipocytes. Furthermore, these kidney-derived cells induced the generation of bone marrow-derived dendritic cells with significantly reduced MHC II expression, increased CD80 expression, increased IL-10 production and the inability to stimulate CD4+ T cell proliferation in allogeneic and nominal antigen-specific cultures. Experiments in mixed and transwell cultures demonstrated that the production of soluble immune modulators, such as IL-6, was responsible for these effects on dendritic cell differentiation and maturation. Contact-dependent mechanisms, however, inhibited mitogenic T cell proliferation. In summary, kidney-derived cells may suppress inflammation in the kidney in vivo; a better understanding of their biology could have therapeutic implications in a wide variety of immune-mediated kidney diseases.

Original languageEnglish (US)
Pages (from-to)831-841
Number of pages11
JournalJournal of the American Society of Nephrology
Volume20
Issue number4
DOIs
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Nephrology

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