Altered endochondral ossification in collagen X mouse models leads to impaired immune responses.
Disruption of collagen X function in hypertrophic cartilage undergoing endochondral ossification was previously linked to altered hematopoiesis in collagen X transgenic (Tg) and null (KO) mice (Jacenko et al., [2002] Am J Pathol 160:2019-2034). Mice displayed altered growth plates, diminished trabecular bone, and marrow hypoplasia with an aberrant lymphocyte profile throughout life. This study identifies altered B220+, CD4+, and CD8+ lymphocyte numbers, as well as CD4+/fox3P+ T regulatory cells in the collagen X mice. Additionally, diminished in vitro splenocyte responses to mitogens and an inability of mice to survive a challenge with Toxoplasma gondii, confirm impaired immune responses. In concert, ELISA and protein arrays identify aberrant levels of inflammatory, chemo-attractant, and matrix binding cytokines in collagen X mouse sera. These data link the disruption of collagen X function in the chondro-osseous junction to an altered hematopoietic stem cell niche in the marrow, resulting in impaired immune function.
Sweeney
E
E
Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania 19104-6046, USA.
Campbell
M
M
Watkins
K
K
Hunter
C A
CA
Jacenko
O
O
D000818:Animals; D024121:Collagen Type X / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D018507:Gene Expression Regulation, Developmental; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology; D018448:Models, Immunological; D010012:Osteogenesis; D015996:Survival Rate; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology
D024121:Collagen Type X; D016207:Cytokines; D008934:Mitogens