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Blood, 1 August 2007, Vol. 110, No. 3, pp. 946-953.
Prepublished online as a Blood First Edition Paper on April 19, 2007; DOI 10.1182/blood-2006-07-036889.
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IMMUNOBIOLOGY
Mast cells are crucial for early inflammation, migration of Langerhans cells, and CTL responses following topical application of TLR7 ligand in mice
Valeska Heib1,
Marc Becker1,
Tobias Warger1,
Gerd Rechtsteiner1,
Christine Tertilt1,
Matthias Klein1,
Tobias Bopp1,
Christian Taube2,
Hansjörg Schild1,
Edgar Schmitt1, and
Michael Stassen1
1 Institute for Immunology and
2 III Medical Clinic, University of Mainz, Mainz, Germany
Until recently, IgE-activated mast cells have been regarded merely as effector cells of adaptive immune responses, involved in allergic reactions and mucosal immunity to parasites. Herein, we report that murine dermal mast cells, activated by local administration of a cream containing the synthetic TLR7 ligand imiquimod, are essential to initiate an early inflammatory reaction. The mast-cell–derived cytokines TNF- and IL-1ß play an important role in this process. Furthermore, TLR7-activated mast cells are also able to promote the emigration of Langerhans cells, which partly depends on the expression of mast-cell–derived IL-1ß. We have previously shown that TLR7 ligation enhances transcutaneous immunization evoked by topical application of vaccine antigens to the skin, a procedure that directly targets skin-resident antigen-presenting cells. Consequently, we now demonstrate here that the capacity to mount a peptide-specific cytotoxic T-lymphocyte response following transcutaneous immunization using imiquimod as adjuvant is severely impaired in mast-cell–deficient mice. Thus, these findings demonstrate the potent versability of alternatively activated mast cells at the interface of innate and adaptive immunity.

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