TY - JOUR
T1 - Regulatory T cell-mediated resolution of lung injury
T2 - Identification of potential target genes via expression profiling
AU - Aggarwal, Neil R.
AU - D'Alessio, Franco R.
AU - Tsushima, Kenji
AU - Sidhaye, Venkataramana K.
AU - Cheadle, Christopher
AU - Grigoryev, Dmitry N.
AU - Barnes, Kathleen C.
AU - King, Landon S.
PY - 2010/4
Y1 - 2010/4
N2 - In animal models of acute lung injury (ALI), gene expression studies have focused on the acute phase of illness, with little emphasis on resolution. In this study, the acute phase of intratracheal lipopolysaccharide (IT LPS)-induced lung injury was similar in wild-type (WT) and recombinase-activating gene-1-deficient (Rag-1-/-) lymphocyte-deficient mice, but resolution was impaired and resolution-phase lung gene expression remained different from baseline only in Rag-1-/- mice. By focusing on groups of genes involved in similar biological processes (gene ontologies) pertinent to inflammation and the immune response, we identified 102 genes at days 4 and 10 after IT LPS with significantly different expression between WT and Rag-1 -/- mice. After adoptive transfer of isolated CD4+CD25+Foxp3+ regulatory T cells (Tregs) to Rag-1-/- mice at the time of IT LPS, resolution was similar to that in WT mice. Of the 102 genes distinctly changed in either WT or Rag-1-/- mice from our 7 gene ontologies, 19 genes reverted from the Rag-1-/- to the WT pattern of expression after adoptive transfer of Tregs, implicating those 19 genes in Treg-mediated resolution of ALI.
AB - In animal models of acute lung injury (ALI), gene expression studies have focused on the acute phase of illness, with little emphasis on resolution. In this study, the acute phase of intratracheal lipopolysaccharide (IT LPS)-induced lung injury was similar in wild-type (WT) and recombinase-activating gene-1-deficient (Rag-1-/-) lymphocyte-deficient mice, but resolution was impaired and resolution-phase lung gene expression remained different from baseline only in Rag-1-/- mice. By focusing on groups of genes involved in similar biological processes (gene ontologies) pertinent to inflammation and the immune response, we identified 102 genes at days 4 and 10 after IT LPS with significantly different expression between WT and Rag-1 -/- mice. After adoptive transfer of isolated CD4+CD25+Foxp3+ regulatory T cells (Tregs) to Rag-1-/- mice at the time of IT LPS, resolution was similar to that in WT mice. Of the 102 genes distinctly changed in either WT or Rag-1-/- mice from our 7 gene ontologies, 19 genes reverted from the Rag-1-/- to the WT pattern of expression after adoptive transfer of Tregs, implicating those 19 genes in Treg-mediated resolution of ALI.
KW - Mouse
KW - Repair
KW - T lymphocyte
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U2 - 10.1152/physiolgenomics.00131.2009
DO - 10.1152/physiolgenomics.00131.2009
M3 - Article
C2 - 20028937
AN - SCOPUS:77951194370
SN - 1094-8341
VL - 41
SP - 109
EP - 119
JO - Physiological Genomics
JF - Physiological Genomics
IS - 2
ER -