Abstract
Interleukin (IL)-33 is an alarmin factor that is highly secreted in a variety of autoimmune diseases, induces maturation of dendritic cells (DCs) and differentiation of T helper 17 (Th17) cells. As the balance between Th17 cells and regulatory T cells (Tregs) is important to maintain immune homeostasis, in this study, we investigated the effects of IL-33 on Treg cell response. We observed that direct treatment with IL-33 had no effect on Treg differentiation, whereas IL-33-matured DCs (IL33-matDCs) inhibited the differentiation of CD4+ T cells to Tregs by decreasing the expression of Foxp3. Furthermore, co-culture with IL-33-matDCs changed stable Tregs (CD25hiCD4+ Tregs) to IL-17-producing cells, whereas IL-33-matDCs had little effects on unstable Tregs (CD25loCD4+ Tregs). The stable Tregs were demonstrated to express high levels of IL-6 receptors. Blocking of IL-6 secreted from IL-33-matDCs suppressed the conversion of Tregs to Th17 cells, indicating the greater propensity to convert stable Tregs to Th17 cells is due to IL-6 signaling. Taken together, these results demonstrate that IL-33 inhibits Treg differentiation and the conversion of stable Tregs to Th17 cells via DCs.
| Original language | English |
|---|---|
| Pages (from-to) | 5-10 |
| Number of pages | 6 |
| Journal | Immunology Letters |
| Volume | 218 |
| DOIs | |
| Publication status | Published - 2020 Feb |
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Keywords
- IL-33
- IL-6 signaling
- Matured DCs
- Th17 cells
- Treg conversion
- Treg differentiation
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
IL-33 changes CD25hi Tregs to Th17 cells through a dendritic cell-mediated pathway. / Park, Su Ho; Jung, Hak Jun; Kim, Tae Sung.
In: Immunology Letters, Vol. 218, 02.2020, p. 5-10.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - IL-33 changes CD25hi Tregs to Th17 cells through a dendritic cell-mediated pathway
AU - Park, Su Ho
AU - Jung, Hak Jun
AU - Kim, Tae Sung
PY - 2020/2
Y1 - 2020/2
N2 - Interleukin (IL)-33 is an alarmin factor that is highly secreted in a variety of autoimmune diseases, induces maturation of dendritic cells (DCs) and differentiation of T helper 17 (Th17) cells. As the balance between Th17 cells and regulatory T cells (Tregs) is important to maintain immune homeostasis, in this study, we investigated the effects of IL-33 on Treg cell response. We observed that direct treatment with IL-33 had no effect on Treg differentiation, whereas IL-33-matured DCs (IL33-matDCs) inhibited the differentiation of CD4+ T cells to Tregs by decreasing the expression of Foxp3. Furthermore, co-culture with IL-33-matDCs changed stable Tregs (CD25hiCD4+ Tregs) to IL-17-producing cells, whereas IL-33-matDCs had little effects on unstable Tregs (CD25loCD4+ Tregs). The stable Tregs were demonstrated to express high levels of IL-6 receptors. Blocking of IL-6 secreted from IL-33-matDCs suppressed the conversion of Tregs to Th17 cells, indicating the greater propensity to convert stable Tregs to Th17 cells is due to IL-6 signaling. Taken together, these results demonstrate that IL-33 inhibits Treg differentiation and the conversion of stable Tregs to Th17 cells via DCs.
AB - Interleukin (IL)-33 is an alarmin factor that is highly secreted in a variety of autoimmune diseases, induces maturation of dendritic cells (DCs) and differentiation of T helper 17 (Th17) cells. As the balance between Th17 cells and regulatory T cells (Tregs) is important to maintain immune homeostasis, in this study, we investigated the effects of IL-33 on Treg cell response. We observed that direct treatment with IL-33 had no effect on Treg differentiation, whereas IL-33-matured DCs (IL33-matDCs) inhibited the differentiation of CD4+ T cells to Tregs by decreasing the expression of Foxp3. Furthermore, co-culture with IL-33-matDCs changed stable Tregs (CD25hiCD4+ Tregs) to IL-17-producing cells, whereas IL-33-matDCs had little effects on unstable Tregs (CD25loCD4+ Tregs). The stable Tregs were demonstrated to express high levels of IL-6 receptors. Blocking of IL-6 secreted from IL-33-matDCs suppressed the conversion of Tregs to Th17 cells, indicating the greater propensity to convert stable Tregs to Th17 cells is due to IL-6 signaling. Taken together, these results demonstrate that IL-33 inhibits Treg differentiation and the conversion of stable Tregs to Th17 cells via DCs.
KW - IL-33
KW - IL-6 signaling
KW - Matured DCs
KW - Th17 cells
KW - Treg conversion
KW - Treg differentiation
UR - http://www.scopus.com/inward/record.url?scp=85076717357&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076717357&partnerID=8YFLogxK
U2 - 10.1016/j.imlet.2019.12.003
DO - 10.1016/j.imlet.2019.12.003
M3 - Article
C2 - 31863784
AN - SCOPUS:85076717357
VL - 218
SP - 5
EP - 10
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
ER -