Abstract
Extracorporeal photochemotherapy (ECP) is a widely used method for either immunization against cutaneous T cell lymphoma or immunosuppression of graft- versus-host disease and organ transplant rejection (OTR). Leukapheresed blood is routed through a chamber, in which 8-methoxypsoralen is activated by ultraviolet energy (PUVA), thereby causing DNA crosslinks in processed leukocytes. Return of ECP-processed mononuclear leukocytes to the patient then modulates aberrant T cell immunity. Since interaction with the ECP flow chamber induces monocyte-to-dendritic antigen presenting cell (DC) maturation, we examined the possibility that PUVA may direct the most heavily exposed monocytes to differentiate into tolerogenic DC, while the least exposed DC might remain immunogenic. Expression of the glucocorticoid-induced leucine zipper (GILZ) gene is a distinguishing marker of tolerogenic DC. We report that PUVA directly stimulates GILZ expression. PUVA-exposed DC up-regulated GILZ, down-regulated costimulatory CD80 and CD86, became resistant to Toll-like receptor-induced maturation, increased IL-10 production and decreased IL-12p70 production, all features of immunosuppressive DC. Knockdown of GILZ with siRNA reduced IL-10 and increased IL-12p70 production, demonstrating that GILZ is critical for this profile. PUVA-induction of GILZ expression by DC may help explain how ECP suppresses GVHD and OTR. Conversely, those ECP-processed monocytes minimally exposed to PUVA may mediate ECP's immunogenic effects.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 379-387 |
| Number of pages | 9 |
| Journal | Transfusion and Apheresis Science |
| Volume | 50 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 1 2014 |
Fingerprint
Keywords
- Dendritic cells
- Extracorporeal photochemotherapy
- GILZ
- Immunoregulation
- Regulatory T cells
ASJC Scopus subject areas
- Hematology
Cite this
}
Activation of GILZ gene by photoactivated 8-methoxypsoralen : Potential role of immunoregulatory dendritic cells in extracorporeal photochemotherapy. / Futterleib, Jeffrey S.; Feng, Hao; Tigelaar, Robert E.; Choi, Jaehyuk; Edelson, Richard L.
In: Transfusion and Apheresis Science, Vol. 50, No. 3, 01.01.2014, p. 379-387.Research output: Contribution to journal › Article
TY - JOUR
T1 - Activation of GILZ gene by photoactivated 8-methoxypsoralen
T2 - Potential role of immunoregulatory dendritic cells in extracorporeal photochemotherapy
AU - Futterleib, Jeffrey S.
AU - Feng, Hao
AU - Tigelaar, Robert E.
AU - Choi, Jaehyuk
AU - Edelson, Richard L.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Extracorporeal photochemotherapy (ECP) is a widely used method for either immunization against cutaneous T cell lymphoma or immunosuppression of graft- versus-host disease and organ transplant rejection (OTR). Leukapheresed blood is routed through a chamber, in which 8-methoxypsoralen is activated by ultraviolet energy (PUVA), thereby causing DNA crosslinks in processed leukocytes. Return of ECP-processed mononuclear leukocytes to the patient then modulates aberrant T cell immunity. Since interaction with the ECP flow chamber induces monocyte-to-dendritic antigen presenting cell (DC) maturation, we examined the possibility that PUVA may direct the most heavily exposed monocytes to differentiate into tolerogenic DC, while the least exposed DC might remain immunogenic. Expression of the glucocorticoid-induced leucine zipper (GILZ) gene is a distinguishing marker of tolerogenic DC. We report that PUVA directly stimulates GILZ expression. PUVA-exposed DC up-regulated GILZ, down-regulated costimulatory CD80 and CD86, became resistant to Toll-like receptor-induced maturation, increased IL-10 production and decreased IL-12p70 production, all features of immunosuppressive DC. Knockdown of GILZ with siRNA reduced IL-10 and increased IL-12p70 production, demonstrating that GILZ is critical for this profile. PUVA-induction of GILZ expression by DC may help explain how ECP suppresses GVHD and OTR. Conversely, those ECP-processed monocytes minimally exposed to PUVA may mediate ECP's immunogenic effects.
AB - Extracorporeal photochemotherapy (ECP) is a widely used method for either immunization against cutaneous T cell lymphoma or immunosuppression of graft- versus-host disease and organ transplant rejection (OTR). Leukapheresed blood is routed through a chamber, in which 8-methoxypsoralen is activated by ultraviolet energy (PUVA), thereby causing DNA crosslinks in processed leukocytes. Return of ECP-processed mononuclear leukocytes to the patient then modulates aberrant T cell immunity. Since interaction with the ECP flow chamber induces monocyte-to-dendritic antigen presenting cell (DC) maturation, we examined the possibility that PUVA may direct the most heavily exposed monocytes to differentiate into tolerogenic DC, while the least exposed DC might remain immunogenic. Expression of the glucocorticoid-induced leucine zipper (GILZ) gene is a distinguishing marker of tolerogenic DC. We report that PUVA directly stimulates GILZ expression. PUVA-exposed DC up-regulated GILZ, down-regulated costimulatory CD80 and CD86, became resistant to Toll-like receptor-induced maturation, increased IL-10 production and decreased IL-12p70 production, all features of immunosuppressive DC. Knockdown of GILZ with siRNA reduced IL-10 and increased IL-12p70 production, demonstrating that GILZ is critical for this profile. PUVA-induction of GILZ expression by DC may help explain how ECP suppresses GVHD and OTR. Conversely, those ECP-processed monocytes minimally exposed to PUVA may mediate ECP's immunogenic effects.
KW - Dendritic cells
KW - Extracorporeal photochemotherapy
KW - GILZ
KW - Immunoregulation
KW - Regulatory T cells
UR - http://www.scopus.com/inward/record.url?scp=84926095092&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926095092&partnerID=8YFLogxK
U2 - 10.1016/j.transci.2013.10.003
DO - 10.1016/j.transci.2013.10.003
M3 - Article
C2 - 24215840
AN - SCOPUS:84926095092
VL - 50
SP - 379
EP - 387
JO - Transfusion and Apheresis Science
JF - Transfusion and Apheresis Science
SN - 1473-0502
IS - 3
ER -