Synoviocytes and skin fibroblasts show opposite effects on IL-23 production and IL-23 receptor expression during cell interactions with immune cells
Abstract Background The IL-23/IL-17 axis is involved in inflammatory diseases including arthritis and psoriasis. However, the response to IL-23 or IL-17 inhibitors is different depending on the disease. The aim was to compare the effects of interactions between immune and stromal cells on the IL-23...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02904-9 |
| _version_ | 1811273730803892224 |
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| author | Mélissa Noack Pierre Miossec |
| author_facet | Mélissa Noack Pierre Miossec |
| author_sort | Mélissa Noack |
| collection | DOAJ |
| description | Abstract Background The IL-23/IL-17 axis is involved in inflammatory diseases including arthritis and psoriasis. However, the response to IL-23 or IL-17 inhibitors is different depending on the disease. The aim was to compare the effects of interactions between immune and stromal cells on the IL-23 axis to understand these differences. Methods Peripheral blood mononuclear cells were co-cultured with RA synoviocytes or Pso skin fibroblasts, with or without phytohemagglutinin, IL-23, or anti-IL-23 antibody. Production of IL-6, IL-1β, IL-23, IL-17, IL-12, and IFNγ was measured by ELISA. IL-23 and cytokine receptor gene expression (IL-17RA, IL-17RC, IL-12Rβ1, IL-12Rβ2, and IL-23R) was analyzed by RT-qPCR. IL-12Rβ1 and IL-23R subunits were analyzed by flow cytometry. Results The production of IL-6, IL-1β, IL-17, IL-12, and IFNγ with synoviocytes or skin fibroblasts was rather similar, and cell interactions with immune cells increased their production, specifically that of IL-17. A major difference was observed for IL-23. Interactions with synoviocytes but not with skin fibroblasts decreased IL-23 secretion while mRNA level was increased, mainly with synoviocytes, reflecting a major consumption difference. IL-23 addition had only one effect, the increase of IL-17 secretion. Cell activation induced similar effects on cytokine receptor gene expression in co-cultures with synoviocytes or skin fibroblasts. The key difference was the cell interaction effects depending on the stromal cell origin. Interactions with synoviocytes increased the expression of both IL-23 receptor subunits at mRNA levels and IL-23R at the surface expression level while interactions with skin fibroblasts decreased their expression at the mRNA level and had no effect at the surface expression level. Conclusion Interactions between immune and stromal cells are crucial in cytokine production and their receptor expression. The origin of stromal cells had a major influence on the production of IL-23 and its receptor expression. Such differences may explain part of the heterogeneity in treatment response. |
| first_indexed | 2024-04-12T23:04:42Z |
| format | Article |
| id | doaj.art-6e4a660ec2064be1ada1ae2367868419 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-12T23:04:42Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-6e4a660ec2064be1ada1ae23678684192022-12-22T03:12:57ZengBMCArthritis Research & Therapy1478-63622022-09-0124111410.1186/s13075-022-02904-9Synoviocytes and skin fibroblasts show opposite effects on IL-23 production and IL-23 receptor expression during cell interactions with immune cellsMélissa Noack0Pierre Miossec1Immunogenomics and Inflammation Research Unit, Edouard Herriot Hospital, Hospices Civils de Lyon and University of LyonImmunogenomics and Inflammation Research Unit, Edouard Herriot Hospital, Hospices Civils de Lyon and University of LyonAbstract Background The IL-23/IL-17 axis is involved in inflammatory diseases including arthritis and psoriasis. However, the response to IL-23 or IL-17 inhibitors is different depending on the disease. The aim was to compare the effects of interactions between immune and stromal cells on the IL-23 axis to understand these differences. Methods Peripheral blood mononuclear cells were co-cultured with RA synoviocytes or Pso skin fibroblasts, with or without phytohemagglutinin, IL-23, or anti-IL-23 antibody. Production of IL-6, IL-1β, IL-23, IL-17, IL-12, and IFNγ was measured by ELISA. IL-23 and cytokine receptor gene expression (IL-17RA, IL-17RC, IL-12Rβ1, IL-12Rβ2, and IL-23R) was analyzed by RT-qPCR. IL-12Rβ1 and IL-23R subunits were analyzed by flow cytometry. Results The production of IL-6, IL-1β, IL-17, IL-12, and IFNγ with synoviocytes or skin fibroblasts was rather similar, and cell interactions with immune cells increased their production, specifically that of IL-17. A major difference was observed for IL-23. Interactions with synoviocytes but not with skin fibroblasts decreased IL-23 secretion while mRNA level was increased, mainly with synoviocytes, reflecting a major consumption difference. IL-23 addition had only one effect, the increase of IL-17 secretion. Cell activation induced similar effects on cytokine receptor gene expression in co-cultures with synoviocytes or skin fibroblasts. The key difference was the cell interaction effects depending on the stromal cell origin. Interactions with synoviocytes increased the expression of both IL-23 receptor subunits at mRNA levels and IL-23R at the surface expression level while interactions with skin fibroblasts decreased their expression at the mRNA level and had no effect at the surface expression level. Conclusion Interactions between immune and stromal cells are crucial in cytokine production and their receptor expression. The origin of stromal cells had a major influence on the production of IL-23 and its receptor expression. Such differences may explain part of the heterogeneity in treatment response.https://doi.org/10.1186/s13075-022-02904-9Cell interactionsStromal cell originIL-23 axisTreatment response |
| spellingShingle | Mélissa Noack Pierre Miossec Synoviocytes and skin fibroblasts show opposite effects on IL-23 production and IL-23 receptor expression during cell interactions with immune cells Arthritis Research & Therapy Cell interactions Stromal cell origin IL-23 axis Treatment response |
| title | Synoviocytes and skin fibroblasts show opposite effects on IL-23 production and IL-23 receptor expression during cell interactions with immune cells |
| title_full | Synoviocytes and skin fibroblasts show opposite effects on IL-23 production and IL-23 receptor expression during cell interactions with immune cells |
| title_fullStr | Synoviocytes and skin fibroblasts show opposite effects on IL-23 production and IL-23 receptor expression during cell interactions with immune cells |
| title_full_unstemmed | Synoviocytes and skin fibroblasts show opposite effects on IL-23 production and IL-23 receptor expression during cell interactions with immune cells |
| title_short | Synoviocytes and skin fibroblasts show opposite effects on IL-23 production and IL-23 receptor expression during cell interactions with immune cells |
| title_sort | synoviocytes and skin fibroblasts show opposite effects on il 23 production and il 23 receptor expression during cell interactions with immune cells |
| topic | Cell interactions Stromal cell origin IL-23 axis Treatment response |
| url | https://doi.org/10.1186/s13075-022-02904-9 |
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