TY - JOUR
T1 - Kidney-derived stromal cells modulate dendritic and T cell responses
AU - Huang, Yanfei
AU - Johnston, Peter
AU - Zhang, Borui
AU - Zakari, Asif
AU - Chowdhry, Tayseer
AU - Smith, Rachel Ruckdeschel
AU - Marbán, Eduardo
AU - Rabb, Hamid
AU - Womer, Karl L.
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2008030310
DO - 10.1681/ASN.2008030310
M3 - Article
C2 - 19297559
AN - SCOPUS:65249155952
SN - 1046-6673
VL - 20
SP - 831
EP - 841
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 4
ER -