Paneth Cells Are a Constitutive Source of IL-10 in Mouse Small Intestinal Organoids
The healthy gut masks a dynamic balance between pro- and anti-inflammatory activities, largely due to microbial factors in the lumen. IL-10 is vital among the anti-inflammatory mediators, yet confirming constitutive versus stimulated secretion in any cell type is difficult due to the cellular comple...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
|
| Series: | Organoids |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2674-1172/4/1/4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850090978930589696 |
|---|---|
| author | Huong Nguyen Francesca Di Cara Jun Wang Andrew W. Stadnyk |
| author_facet | Huong Nguyen Francesca Di Cara Jun Wang Andrew W. Stadnyk |
| author_sort | Huong Nguyen |
| collection | DOAJ |
| description | The healthy gut masks a dynamic balance between pro- and anti-inflammatory activities, largely due to microbial factors in the lumen. IL-10 is vital among the anti-inflammatory mediators, yet confirming constitutive versus stimulated secretion in any cell type is difficult due to the cellular complexity in the gut. Seeking to determine whether intestinal epithelial cells are programmed to constitutively make IL-10, we confirmed that IL-10 mRNA was present in enteroids from C57BL/6 mice and IL-10 protein was co-localized with a Paneth cell marker but not with markers for goblet or tuft cells. Paneth cells positive for IL-10 also possessed apical and basal IL-10RA, while cells negative for IL-10 had only basal IL-10RA, suggesting a possible autocrine role for IL-10. Indeed, Paneth cells in IL-10 gene knockout (IL-10KO) enteroids possessed lower levels of anti-microbial protein mRNAs, which could not be restored by adding IL-10. Enteroids passaged onto Transwell<sup>®</sup> filters to form monolayers were treated with IL-10 and STAT3 phosphorylation was measured. Apically applied IL-10 resulted in a stronger STAT3 signal than basally applied cytokine. Our results indicate that a subpopulation of Paneth cells constitutively secrete IL-10 apically, which binds apical IL-10RA, impacting the expression of anti-microbial proteins unique to Paneth cells. |
| format | Article |
| id | doaj-art-04bbddc851c64549b0d4b198f232999d |
| institution | DOAJ |
| issn | 2674-1172 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Organoids |
| spelling | doaj-art-04bbddc851c64549b0d4b198f232999d2025-08-20T02:42:28ZengMDPI AGOrganoids2674-11722025-02-0141410.3390/organoids4010004Paneth Cells Are a Constitutive Source of IL-10 in Mouse Small Intestinal OrganoidsHuong Nguyen0Francesca Di Cara1Jun Wang2Andrew W. Stadnyk3Department of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 4R2, CanadaThe healthy gut masks a dynamic balance between pro- and anti-inflammatory activities, largely due to microbial factors in the lumen. IL-10 is vital among the anti-inflammatory mediators, yet confirming constitutive versus stimulated secretion in any cell type is difficult due to the cellular complexity in the gut. Seeking to determine whether intestinal epithelial cells are programmed to constitutively make IL-10, we confirmed that IL-10 mRNA was present in enteroids from C57BL/6 mice and IL-10 protein was co-localized with a Paneth cell marker but not with markers for goblet or tuft cells. Paneth cells positive for IL-10 also possessed apical and basal IL-10RA, while cells negative for IL-10 had only basal IL-10RA, suggesting a possible autocrine role for IL-10. Indeed, Paneth cells in IL-10 gene knockout (IL-10KO) enteroids possessed lower levels of anti-microbial protein mRNAs, which could not be restored by adding IL-10. Enteroids passaged onto Transwell<sup>®</sup> filters to form monolayers were treated with IL-10 and STAT3 phosphorylation was measured. Apically applied IL-10 resulted in a stronger STAT3 signal than basally applied cytokine. Our results indicate that a subpopulation of Paneth cells constitutively secrete IL-10 apically, which binds apical IL-10RA, impacting the expression of anti-microbial proteins unique to Paneth cells.https://www.mdpi.com/2674-1172/4/1/4organoidPaneth cellinterleukin-10 |
| spellingShingle | Huong Nguyen Francesca Di Cara Jun Wang Andrew W. Stadnyk Paneth Cells Are a Constitutive Source of IL-10 in Mouse Small Intestinal Organoids Organoids organoid Paneth cell interleukin-10 |
| title | Paneth Cells Are a Constitutive Source of IL-10 in Mouse Small Intestinal Organoids |
| title_full | Paneth Cells Are a Constitutive Source of IL-10 in Mouse Small Intestinal Organoids |
| title_fullStr | Paneth Cells Are a Constitutive Source of IL-10 in Mouse Small Intestinal Organoids |
| title_full_unstemmed | Paneth Cells Are a Constitutive Source of IL-10 in Mouse Small Intestinal Organoids |
| title_short | Paneth Cells Are a Constitutive Source of IL-10 in Mouse Small Intestinal Organoids |
| title_sort | paneth cells are a constitutive source of il 10 in mouse small intestinal organoids |
| topic | organoid Paneth cell interleukin-10 |
| url | https://www.mdpi.com/2674-1172/4/1/4 |
| work_keys_str_mv | AT huongnguyen panethcellsareaconstitutivesourceofil10inmousesmallintestinalorganoids AT francescadicara panethcellsareaconstitutivesourceofil10inmousesmallintestinalorganoids AT junwang panethcellsareaconstitutivesourceofil10inmousesmallintestinalorganoids AT andrewwstadnyk panethcellsareaconstitutivesourceofil10inmousesmallintestinalorganoids |