title: Induction of regulatory T cells by a murine β-defensin.
abstract: β-Defensins are antimicrobial peptides of the innate immune system produced in the skin by various stimuli, including proinflammatory cytokines, bacterial infection, and exposure to UV radiation (UVR). In this study we demonstrate that the UVR-inducible antimicrobial peptide murine β-defensin-14 (mBD-14) switches CD4(+)CD25(-) T cells into a regulatory phenotype by inducing the expression of specific markers like Foxp3 and CTLA-4. This is functionally relevant because mBD-14-treated T cells inhibit sensitization upon adoptive transfer into naive C57BL/6 mice. Accordingly, injection of mBD-14, comparable to UVR, suppresses the induction of contact hypersensitivity and induces Ag-specific regulatory T cells (Tregs). Further evidence for the ability of mBD-14 to induce Foxp3(+) T cells is provided using DEREG (depletion of Tregs) mice in which Foxp3-expressing cells can be depleted by injecting diphtheria toxin. mBD-14 does not suppress sensitization in IL-10 knockout mice, suggesting involvement of IL-10 in mBD-14-mediated immunosuppression. However, unlike UVR, mBD-14 does not appear to mediate its immunosuppressive effects by affecting dendritic cells. Accordingly, UVR-induced immunosuppression is not abrogated in mBD-14 knockout mice. Together, these data suggest that mBD-14, like UVR, has the capacity to induce Tregs but does not appear to play a major role in UVR-induced immunosuppression. Through this capacity, mBD-14 may protect the host from microbial attacks on the one hand, but tame T cell-driven reactions on the other hand, thereby enabling an antimicrobial defense without collateral damage by the adaptive immune system.
authors.affiliation: Department of Dermatology and Allergology, University of Kiel, 24105 Kiel, Germany.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Navid
authors.forename: Michele
authors.initials: M
authors.lastname: Boniotto
authors.forename: Catherine
authors.initials: C
authors.lastname: Walker
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ahrens
authors.forename: Ehrhardt
authors.initials: E
authors.lastname: Proksch
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz
authors.forename: Agatha
authors.initials: A
authors.lastname: Schwarz
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D060908:CTLA-4 Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology* / Q000528:radiation effects; D004139:Dinitrofluorobenzene / Q000008:administration & dosage; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D016130:Immunophenotyping; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039921:Neuropilins / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology* / Q000528:radiation effects; D014466:Ultraviolet Rays; D023083:beta-Defensins / Q000008:administration & dosage* / Q000172:deficiency / Q000502:physiology*
chemical_list: D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039921:Neuropilins; D023083:beta-Defensins; C556378:beta-defensin-14, mouse; D004139:Dinitrofluorobenzene