Impaired mast cell-driven immune responses in mice lacking the transcription factor NFATc2.
The three calcium-dependent factors NFATc1, c2, and c3 are expressed in cells of the immune system and play pivotal roles in modulating cellular activation. With regard to NFATc2, it was reported that NFATc2-deficient mice display increased immune responses in several models for infection and allergy in vivo. This led to the assumption that NFATc2 is involved in the maintenance of immune homeostasis. Using the synthetic TLR7 agonist imiquimod as an adjuvant in epicutaneous peptide immunization, we observed that both the inflammatory reaction and the peptide-specific CTL response are severely impaired in NFATc2-deficient mice. Detailed analyses revealed that early production of proinflammatory cytokines, lymph node hypertrophy, and migration of Langerhans cells are strongly reduced in NFATc2-deficient animals. With the aid of mast cell-deficient mice and reconstitution experiments using mast cells derived from either NFATc2-deficient mice or wild-type controls, we were able to show that NFATc2 expressed in mast cells is critical for the initiation of inflammation, migration of Langerhans cells, and the development of full-blown CTL responses following epicutaneous immunization. Thus, NFATc2 is an important factor controlling mast cell accessory function at the interface of innate and adaptive immunity.
Institute for Immunology, University of Mainz, Mainz, Germany.
Marc
M
Becker
Valeska
V
Heib
Matthias
M
Klein
Fatma
F
Doener
Tobias
T
Bopp
Christian
C
Taube
Markus
M
Radsak
Hansjörg
H
Schild
Edgar
E
Schmitt
Michael
M
Stassen
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000276:Adjuvants, Immunologic; D018836:Inflammation Mediators; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse