Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.
OBJECTIVE
During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied.


METHODS
Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD).


RESULTS
Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice.


CONCLUSIONS
Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.
Telethon Kids Institute, University of Western Australia, PO Box 855, West Perth, WA, 6872, Australia.
Naomi M
NM
Scott
Telethon Kids Institute, University of Western Australia, PO Box 855, West Perth, WA, 6872, Australia.
Royce L X
RL
Ng
Telethon Kids Institute, University of Western Australia, PO Box 855, West Perth, WA, 6872, Australia.
Terence A
TA
McGonigle
Telethon Kids Institute, University of Western Australia, PO Box 855, West Perth, WA, 6872, Australia.
Shelley
S
Gorman
Telethon Kids Institute, University of Western Australia, PO Box 855, West Perth, WA, 6872, Australia. Prue.Hart@telethonkids.org.au.
Prue H
PH
Hart
D000281:Administration, Intranasal; D019264:Adoptive Transfer; D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation; D008070:Lipopolysaccharides; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008810:Mice, Inbred C57BL; D009930:Organic Chemicals; D010047:Ovalbumin / Q000276:immunology; D011828:Radiation Chimera; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D012867:Skin / Q000276:immunology
D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D009930:Organic Chemicals; C070080:PKH 26; D007073:Immunoglobulin E; D000077209:Decitabine; D010047:Ovalbumin; D015254:DNA Modification Methylases; D016650:Fluorescein-5-isothiocyanate; D001374:Azacitidine
Bone marrow; Chimeric mice; Dendritic cells; Immunoregulatory; Respiratory inflammation