TH9 cells are required for tissue mast cell accumulation during allergic inflammation.
BACKGROUND
IL-9 is important for the growth and survival of mast cells. IL-9 is produced by T cells, natural killer T cells, mast cells, eosinophils, and innate lymphoid cells, although the cells required for mast cell accumulation during allergic inflammation remain undefined.


OBJECTIVE
We sought to elucidate the role of TH9 cells in promoting mast cell accumulation in models of allergic lung inflammation.


METHODS
Adoptive transfer of ovalbumin-specific TH2 and TH9 cells was used to assess the ability of each subset to mediate mast cell accumulation in tissues. Mast cell accumulation was assessed in wild-type mice and mice with PU.1-deficient T cells subjected to acute and chronic models of allergic inflammation.


RESULTS
Adoptive transfer experiments demonstrated that recipients of TH9 cells had significantly higher mast cell accumulation and expression of mast cell proteases compared with control or TH2 recipients. Mast cell accumulation was dependent on IL-9, but not IL-13, a cytokine required for many aspects of allergic inflammation. In models of acute and chronic allergic inflammation, decreased IL-9 levels in mice with PU.1-deficient T cells corresponded to diminished tissue mast cell numbers and expression of mast cell proteases. Mice with PU.1-deficient T cells have defects in IL-9 production from CD4(+) T cells, but not natural killer T cells or innate lymphoid cells, suggesting a TH cell-dependent phenotype. Rag1(-/-) mice subjected to a chronic model of allergic inflammation displayed reduced mast cell infiltration comparable with accumulation in mice with PU.1-deficient T cells, emphasizing the importance of IL-9 produced by T cells in mast cell recruitment.


CONCLUSIONS
TH9 cells are a major source of IL-9 in models of allergic inflammation and play an important role in mast cell accumulation and activation.
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind.
Sarita
S
Sehra
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind.
Weiguo
W
Yao
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind.
Evelyn T
ET
Nguyen
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind.
Nicole L
NL
Glosson-Byers
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind.
Nahid
N
Akhtar
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind.
Baohua
B
Zhou
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind. Electronic address: mkaplan2@iupui.edu.
Mark H
MH
Kaplan
D019264:Adoptive Transfer; D000818:Animals; D019070:Cell Lineage / Q000276:immunology; D002465:Cell Movement; D021181:Egg Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D000099232:Proto-Oncogene Protein Spi-1
D018398:Homeodomain Proteins; D018793:Interleukin-13; D016906:Interleukin-9; D010047:Ovalbumin; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C064658:RAG-1 protein
PU.1; T(H)2 cells; T(H)9 cells; allergic inflammation; mast cells