Accelerated dendritic-cell migration and T-cell priming in SPARC-deficient mice.
On their path to draining lymph nodes, epidermal Langerhans cells traverse collagen-dense connective tissue before reaching lymphatic vessels. The matricellular protein SPARC (secreted protein, acidic and rich in cysteine), which is induced during inflammation and tissue repair, organizes collagen deposition in tissue stroma. We analyzed Langerhans cell and dendritic-cell migration and its impact on T-cell priming in SPARC-null (SPARC(-/-)) and SPARC-sufficient (SPARC(+/+)) mice. Although the same number of Langerhans cells populate the ear skin of SPARC(-/-) and SPARC(+/+) mice, more Langerhans cells were found in the lymph nodes draining antigen-sensitized ears of SPARC(-/-) mice and significantly more Langerhans cells migrated from null-mice-derived ear skin explants. Such favored Langerhans cell migration is due to the host environment, as demonstrated by SPARC(+/+)>SPARC(-/-) and reciprocal chimeras, and have a profound influence on T-cell priming. Contact-, delayed type-hypersensitivity and naive T-cell receptor-transgenic T-cell priming, together indicate that the lack of SPARC in the environment accelerates the onset of T-cell priming by hastening Langerhans cell/dendritic-cell migration.
Sangaletti
Sabina
S
Immunotherapy and Gene Therapy Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milano, Italy.
Gioiosa
Lucia
L
Guiducci
Cristiana
C
Rotta
Gianluca
G
Rescigno
Maria
M
Stoppacciaro
Antonella
A
Chiodoni
Claudia
C
Colombo
Mario P
MP
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000235:genetics; D002465:Cell Movement / Q000235:genetics* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D015676:Osteonectin / Q000235:genetics*; D012867:Skin / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D015676:Osteonectin