Antigen-induced increases in pulmonary mast cell progenitor numbers depend on IL-9 and CD1d-restricted NKT cells.
Pulmonary mast cell progenitor (MCp) numbers increase dramatically in sensitized and aerosolized Ag-challenged mice. This increase depends on CD4(+) T cells, as no MCp increase occurs in the lungs of sensitized wild-type (WT) mice after mAb depletion of CD4(+) but not CD8(+) cells before aerosol Ag challenge. Neither the genetic absence of IL-4, IL-4Ralpha chain, STAT-6, IFN-gamma, or IL-12p40 nor mAb blockade of IFN-gamma, IL-3, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-12p40, or IL-12p40Rbeta1 before Ag challenge in WT mice reduces the pulmonary MCp increase. However, sensitized and Ag-challenged IL-9-deficient mice and sensitized WT mice given mAb to IL-9 just before Ag challenge show significant reductions in elicited lung MCp/10(6) mononuclear cells of 47 and 66%, respectively. CD1d-deficient mice and WT mice receiving anti-CD1d before Ag challenge also show significant reductions of 65 and 59%, respectively, in elicited lung MCp/10(6) mononuclear cells, revealing an additional requirement for MCp recruitment. However, in Jalpha18-deficient mice, which lack only type 1 or invariant NKT cells, the increase in the numbers of lung MCp with Ag challenge was intact, indicating that their recruitment must be mediated by type 2 NKT cells. Furthermore, anti-CD1d treatment of IL-9-deficient mice or anti-IL-9 treatment of CD1d-deficient mice does not further reduce the significant partial impairment of MCp recruitment occurring with a single deficiency. These findings implicate type 2 NKT cells and IL-9 as central regulators that function in the same pathway mediating the Ag-induced increase in numbers of pulmonary MCp.
Division of Rheumatology, Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Tatiana G
TG
Jones
Jenny
J
Hallgren
Alison
A
Humbles
Timothy
T
Burwell
Fred D
FD
Finkelman
Pilar
P
Alcaide
K Frank
KF
Austen
Michael F
MF
Gurish
D000336:Aerosols; D000818:Animals; D000906:Antibodies / Q000276:immunology; D055610:Antigens, CD1d / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013234:Stem Cells / Q000276:immunology*
D000336:Aerosols; D000906:Antibodies; D055610:Antigens, CD1d; D004268:DNA-Binding Proteins; D016906:Interleukin-9; C499308:Rag2 protein, mouse; D010047:Ovalbumin