B cell receptor-induced IL-10 production from neonatal mouse CD19+CD43- cells depends on STAT5-mediated IL-6 secretion
Newborns are unable to reach the adult-level humoral immune response partly due to the potent immunoregulatory role of IL-10. Increased IL-10 production by neonatal B cells has been attributed to the larger population of IL-10-producting CD43+ B-1 cells in neonates. Here, we show that neonatal mouse CD43- non-B-1 cells also produce substantial amounts of IL-10 following B cell antigen receptor (BCR) activation. In neonatal mouse CD43- non-B-1 cells, BCR engagement activated STAT5 under the control of phosphorylated forms of signaling molecules Syk, Btk, PKC, FAK, and Rac1. Neonatal STAT5 activation led to IL-6 production, which in turn was responsible for IL-10 production in an autocrine/paracrine fashion through the activation of STAT3. In addition to the increased IL-6 production in response to BCR stimulation, elevated expression of IL-6Rα expression in neonatal B cells rendered them highly susceptible to IL-6-mediated STAT3 phosphorylation and IL-10 production. Finally, IL-10 secreted from neonatal mouse CD43- non-B-1 cells was sufficient to inhibit TNF-α secretion by macrophages. Our results unveil a distinct mechanism of IL-6-dependent IL-10 production in BCR-stimulated neonatal CD19+CD43- B cells.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
eLife - 12(2023) vom: 03. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sakai, Jiro [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 24.02.2023 Date Revised 28.02.2023 published: Electronic GEO: GSE200955 Citation Status MEDLINE |
|---|
| doi: |
10.7554/eLife.83561 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM352453443 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM352453443 | ||
| 003 | DE-627 | ||
| 005 | 20231226053748.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.7554/eLife.83561 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1174.xml |
| 035 | |a (DE-627)NLM352453443 | ||
| 035 | |a (NLM)36735294 | ||
| 035 | |a (PII)e83561 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sakai, Jiro |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a B cell receptor-induced IL-10 production from neonatal mouse CD19+CD43- cells depends on STAT5-mediated IL-6 secretion |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 24.02.2023 | ||
| 500 | |a Date Revised 28.02.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a GEO: GSE200955 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Newborns are unable to reach the adult-level humoral immune response partly due to the potent immunoregulatory role of IL-10. Increased IL-10 production by neonatal B cells has been attributed to the larger population of IL-10-producting CD43+ B-1 cells in neonates. Here, we show that neonatal mouse CD43- non-B-1 cells also produce substantial amounts of IL-10 following B cell antigen receptor (BCR) activation. In neonatal mouse CD43- non-B-1 cells, BCR engagement activated STAT5 under the control of phosphorylated forms of signaling molecules Syk, Btk, PKC, FAK, and Rac1. Neonatal STAT5 activation led to IL-6 production, which in turn was responsible for IL-10 production in an autocrine/paracrine fashion through the activation of STAT3. In addition to the increased IL-6 production in response to BCR stimulation, elevated expression of IL-6Rα expression in neonatal B cells rendered them highly susceptible to IL-6-mediated STAT3 phosphorylation and IL-10 production. Finally, IL-10 secreted from neonatal mouse CD43- non-B-1 cells was sufficient to inhibit TNF-α secretion by macrophages. Our results unveil a distinct mechanism of IL-6-dependent IL-10 production in BCR-stimulated neonatal CD19+CD43- B cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 4 | |a B cell | |
| 650 | 4 | |a cytokine | |
| 650 | 4 | |a immunology | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a mouse | |
| 650 | 4 | |a neonate | |
| 650 | 4 | |a signaling | |
| 650 | 4 | |a vaccine | |
| 650 | 7 | |a Antigens, CD19 |2 NLM | |
| 650 | 7 | |a Interleukin-10 |2 NLM | |
| 650 | 7 | |a 130068-27-8 |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a Receptors, Antigen, B-Cell |2 NLM | |
| 650 | 7 | |a STAT5 Transcription Factor |2 NLM | |
| 650 | 7 | |a Leukosialin |2 NLM | |
| 700 | 1 | |a Yang, Jiyeon |e verfasserin |4 aut | |
| 700 | 1 | |a Chou, Chao-Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Wells W |e verfasserin |4 aut | |
| 700 | 1 | |a Akkoyunlu, Mustafa |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t eLife |d 2012 |g 12(2023) vom: 03. Feb. |w (DE-627)NLM221831460 |x 2050-084X |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2023 |g day:03 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.7554/eLife.83561 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2023 |b 03 |c 02 | ||