IL-25 enhances TH17 cell-mediated contact dermatitis by promoting IL-1ß production by dermal dendritic cells.
J Allergy Clin Immunol
; 142(5): 1500-1509.e10, 2018 11.
Article
in En
| MEDLINE
| ID: mdl-29522843
ABSTRACT
BACKGROUND:
In addition to thymic stromal lymphopoietin and IL-33, IL-25 is known to induce TH2 cytokine production by various cell types, including TH2 cells, TH9 cells, invariant natural killer T cells, and group 2 innate lymphoid cells, involved in TH2-type immune responses. Because both TH2-type and TH17-type cells/cytokines are crucial for contact hypersensitivity (CHS), IL-25 can contribute to this by enhancing TH2-type immune responses. However, the precise role of IL-25 in the pathogenesis of fluorescein isothiocyanate-induced CHS is poorly understood.OBJECTIVE:
We investigated the contribution of IL-25 to CHS using Il25-/- mice.METHODS:
CHS was evaluated by means of measurement of ear skin thickness in mice after fluorescein isothiocyanate painting. Skin dendritic cell (DC) migration, hapten-specific TH cell differentiation, and detection of IL-1ß-producing cells were determined by using flow cytometry, ELISA, and immunohistochemistry, respectively.RESULTS:
In contrast to thymic stromal lymphopoietin, we found that IL-25 was not essential for skin DC migration or hapten-specific TH cell differentiation in the sensitization phase of CHS. Unexpectedly, mast cell- and non-immune cell-derived IL-25 was important for hapten-specific TH17 cell-mediated rather than TH2 cell-mediated inflammation in the elicitation phase of CHS by enhancing TH17-related, but not TH2-related, cytokines in the skin. In particular, IL-1ß produced by dermal DCs in response to IL-25 was crucial for hapten-specific TH17 cell activation, contributing to induction of local inflammation in the elicitation phase of CHS.CONCLUSION:
Our results identify a novel IL-25 inflammatory pathway involved in induction of TH17 cell-mediated, but not TH2 cell-mediated, CHS. IL-25 neutralization can be a potential approach for treatment of CHS.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytokines
/
Dermatitis, Allergic Contact
/
Th17 Cells
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2018
Type:
Article
Affiliation country:
Japan