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First published online 26 July 2005
doi: 10.1242/jcs.02474

Journal of Cell Science 118, 3685-3694 (2005)
Published by The Company of Biologists 2005
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Research Article

Accelerated dendritic-cell migration and T-cell priming in SPARC-deficient mice

Sabina Sangaletti1, Lucia Gioiosa1, Cristiana Guiducci1, Gianluca Rotta2, Maria Rescigno2, Antonella Stoppacciaro3, Claudia Chiodoni1 and Mario P. Colombo1,*

1 Immunotherapy and Gene Therapy Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milano, Italy
2 Department of Experimental Oncology, European Institute of Oncology, 20141 Milano, Italy
3 Department of Experimental Medicine and Pathology, 2nd Faculty of Medicine, University of Rome "La Sapienza", Roma, Italy

* Author for correspondence (e-mail: mario.colombo{at}istitutotumori.mi.it)

Accepted 9 May 2005

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.

Key words: DC migration, SPARC, T-cell priming


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