Regulatory T cell-mediated resolution of lung injury: identification of potential target genes via expression profiling.
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.
Aggarwal
Neil R
NR
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21224, USA.
D'Alessio
Franco R
FR
Tsushima
Kenji
K
Sidhaye
Venkataramana K
VK
Cheadle
Christopher
C
Grigoryev
Dmitry N
DN
Barnes
Kathleen C
KC
King
Landon S
LS
D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D019264:Adoptive Transfer; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016000:Cluster Analysis; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D016654:Genes, RAG-1; D008070:Lipopolysaccharides; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D013997:Time Factors; D014945:Wound Healing / Q000235:genetics*
D008070:Lipopolysaccharides; C482199:lipopolysaccharide, E coli O55-B5