TY - JOUR
T1 - Contrasting roles of the IL-1 and IL-18 receptors in MyD88-dependent contact hypersensitivity
AU - Klekotka, Paul A.
AU - Yang, Liping
AU - Yokoyama, Wayne M.
N1 - Funding Information:
We thank Achim Schneeberger for expert technical assistance with the contact hypersensitivity experiments. We would also like to thank Susan Gilfillan and Marco Colonna for providing MyD88-, TLR4-, TLR6-, and TLR9-deficient mice. Work in the Yokoyama laboratory is supported by grants from the National Institute of Allergy and Infectious Diseases and National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS). WMY is an investigator of the Howard Hughes Medical Institute. This study was also supported by National Institutes of Health (NIAMS) grant K08 A1071016–01 to PA Klekotka, as well as grants from the Dermatology Foundation.
PY - 2010/1
Y1 - 2010/1
N2 - Contact hypersensitivity (CHS) requires activation of the innate immune system, and results in an adaptive immune response. Many cells of the innate immune system use Toll-like receptors (TLRs), which signal through the adaptor protein, MyD88, to initiate an immune response. MyD88 is also required for signaling downstream of the IL-1 and Il-18 receptors (IL-1R and IL-18R, respectively). Herein, we studied the MyD88 signaling pathway in the CHS response to DNFB. Mice deficient in MyD88 were unable to mount a CHS response to DNFB. In contrast, mice deficient in Toll/IL-1R-containing adaptor-inducing IFN-Β, TLR2, TLR4, TLR6, and TLR9 had no defect in their ability to respond to DNFB. Although both IL-1R and IL-18R-deficient mice showed a reduced CHS response to DNFB, in bone marrow chimera and adoptive transfer experiments, we found that MyD88 and the IL-18R were required in a radioresistant cell in the sensitization phase of the CHS response. In contrast, similar strategies revealed that the IL-1R was required in a radiosensitive cell in the sensitization phase of the CHS response. Taken together, these data indicate that the IL-1R and IL-18R/MyD88 pathways are required in distinctly different cells during the sensitization phase of CHS.
AB - Contact hypersensitivity (CHS) requires activation of the innate immune system, and results in an adaptive immune response. Many cells of the innate immune system use Toll-like receptors (TLRs), which signal through the adaptor protein, MyD88, to initiate an immune response. MyD88 is also required for signaling downstream of the IL-1 and Il-18 receptors (IL-1R and IL-18R, respectively). Herein, we studied the MyD88 signaling pathway in the CHS response to DNFB. Mice deficient in MyD88 were unable to mount a CHS response to DNFB. In contrast, mice deficient in Toll/IL-1R-containing adaptor-inducing IFN-Β, TLR2, TLR4, TLR6, and TLR9 had no defect in their ability to respond to DNFB. Although both IL-1R and IL-18R-deficient mice showed a reduced CHS response to DNFB, in bone marrow chimera and adoptive transfer experiments, we found that MyD88 and the IL-18R were required in a radioresistant cell in the sensitization phase of the CHS response. In contrast, similar strategies revealed that the IL-1R was required in a radiosensitive cell in the sensitization phase of the CHS response. Taken together, these data indicate that the IL-1R and IL-18R/MyD88 pathways are required in distinctly different cells during the sensitization phase of CHS.
UR - http://www.scopus.com/inward/record.url?scp=72049094542&partnerID=8YFLogxK
U2 - 10.1038/jid.2009.242
DO - 10.1038/jid.2009.242
M3 - Article
C2 - 19657352
AN - SCOPUS:72049094542
VL - 130
SP - 184
EP - 191
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 1
ER -