Complex role of the IL-4 receptor alpha in a murine model of airway inflammation: expression of the IL-4 receptor alpha on nonlymphoid cells of bone marrow origin contributes to severity of inflammation.
Recent studies have suggested the IL-4Ralpha expressed on lung epithelium is necessary for TH2-mediated goblet cell differentiation and mucus hypersecretion in a murine model of allergic lung disease. However, the IL-4Ralpha is expressed on numerous cell types that could contribute to the overall pathology and severity of asthma. The relative role of the receptor on these cells has not yet been conclusively delineated. To dissect the contribution of IL-4Ralpha in the development of pulmonary allergic responses, we generated murine radiation bone marrow (BM) chimeras. BM from IL-4Ralpha(+) or IL-4Ralpha(-) mice was transferred into recipient mice that expressed or lacked IL-4Ralpha. In the absence of IL-4Ralpha in recipient mice, there was no goblet cell metaplasia or mucus hypersecretion in response to OVA, even in the presence of TH2 cells and substantial eosinophilic infiltration. More importantly, we found that expression of the IL-4Ralpha on a nonlymphoid, MHC class II(+), BM-derived cell type contributes to the severity of inflammation and mucus production. These results suggest that IL-4 and IL-13 contribute to the development of allergic inflammation by stimulating a complex interaction between IL-4Ralpha(+) cell types of both bone marrow and non-bone marrow origin.
Kelly-Welch
Ann E
AE
Departments of Immunology, Holland Laboratory, American Red Cross, Rockville, MD 20855, USA.
Melo
Marco E F
ME
Smith
Elizabeth
E
Ford
Andrew Q
AQ
Haudenschild
Christian
C
Noben-Trauth
Nancy
N
Keegan
Achsah D
AD
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology; D006965:Hyperplasia; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009093:Mucus / Q000378:metabolism; D021122:Protein Subunits / Q000096:biosynthesis / Q000502:physiology*; D011828:Radiation Chimera / Q000276:immunology; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology*; D012720:Severity of Illness Index; D018418:Th2 Cells / Q000276:immunology / Q000637:transplantation
D021122:Protein Subunits; D019948:Receptors, Interleukin-4