NLRP3-mediated IL-1β in regulating the imbalance between Th17 and Treg in experimental autoimmune prostatitis.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Prostatitis*/immunology ; Prostatitis*/metabolism ; Prostatitis*/pathology ; NLR Family, Pyrin Domain-Containing 3 Protein*/metabolism ; Interleukin-1beta*/metabolism ; Th17 Cells*/immunology ; Th17 Cells*/metabolism ; T-Lymphocytes, Regulatory*/immunology ; T-Lymphocytes, Regulatory*/metabolism ; Autoimmune Diseases*/immunology ; Autoimmune Diseases*/metabolism ; Disease Models, Animal*; Animals ; Male ; Mice ; STAT3 Transcription Factor/metabolism ; Inflammasomes/metabolism ; Cell Differentiation ; Mice, Inbred C57BL

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a urinary disorder that affects youthful to middle-aged men most frequently. It has been revealed that Th17/Treg imbalance is a crucial factor in the pathophysiological mechanisms behind this disease. However, this imbalance's mechanisms are unknown. In the experimental autoimmune prostatitis (EAP) mouse model, the NLRP3 inflammasome was turned on, IL-1β levels went up. Moreover, there exists a discernible positive association between the upsurge in IL-1β and the perturbation of Th17/Treg equilibrium. Additionally, we have revealed that IL-1β plays a vital role in promoting the differentiation of Naïve CD4+ T cells into the Th17 cells and enhances the conversion of Treg cells into Th17 cells. Further studies revealed that IL-1β promotes STAT3 phosphorylation, which is what causes Treg cells to become Th17 cells. All data strongly suggest that the NLRP3 inflammatory influence Th17 cell development and the conversion of Treg cells into Th17 cells through IL-1β, disrupting the Th17/Treg balance and exacerbating EAP inflammation. In this article, we provide new theories for the pathogenesis of CP/CPPS and propose new prevention and therapy methods.
(© 2024. The Author(s).)

Sci Rep. 2015 Oct 06;5:14674. (PMID: 26441347)
Prostate. 2021 Jan;81(1):29-40. (PMID: 33085775)
Cell. 2010 Mar 19;140(6):821-32. (PMID: 20303873)
Blood. 2005 Apr 1;105(7):2877-86. (PMID: 15613550)
Front Immunol. 2022 May 26;13:875412. (PMID: 35693826)
Prostate. 2021 Nov;81(15):1179-1190. (PMID: 34418127)
Arthritis Rheum. 2013 Dec;65(12):3176-85. (PMID: 24022661)
J Immunol. 2007 Jun 1;178(11):6725-9. (PMID: 17513718)
Prostate. 2018 Jul;78(10):707-713. (PMID: 29577372)
Inflammation. 2019 Oct;42(5):1705-1718. (PMID: 31209730)
J Leukoc Biol. 2014 Jul;96(1):39-48. (PMID: 24744433)
PLoS One. 2015 May 01;10(5):e0125623. (PMID: 25933188)
Annu Rev Immunol. 2009;27:519-50. (PMID: 19302047)
Mol Aspects Med. 2020 Dec;76:100889. (PMID: 32859386)
Annu Rev Immunol. 2012;30:531-64. (PMID: 22224781)
J Immunol Res. 2022 May 25;2022:9444227. (PMID: 35664352)
FASEB J. 2020 Oct;34(10):14006-14023. (PMID: 32862457)
Nat Immunol. 2015 Mar;16(3):286-95. (PMID: 25642823)
Clin Immunol. 2018 Dec;197:154-160. (PMID: 30236770)
Hum Reprod. 2005 Sep;20(9):2567-72. (PMID: 15890732)
Nat Rev Urol. 2014 May;11(5):259-69. (PMID: 24686526)
Trends Mol Med. 2011 Feb;17(2):57-64. (PMID: 21163704)
Nat Immunol. 2018 Jul;19(7):665-673. (PMID: 29925983)
Nat Med. 2014 Jan;20(1):62-8. (PMID: 24362934)
Prostate. 2019 Sep;79(12):1439-1449. (PMID: 31233226)
J Urol. 2009 Aug;182(2):558-63. (PMID: 19524948)
Prostate. 2021 Oct;81(14):1078-1090. (PMID: 34320251)
Immunity. 2009 Apr 17;30(4):576-87. (PMID: 19362022)
J Urol. 2010 Mar;183(3):1213-20. (PMID: 20096883)
J Sex Med. 2014 Dec;11(12):3093-101. (PMID: 25307084)
J Cell Mol Med. 2020 Dec;24(23):14099-14109. (PMID: 33124198)
Semin Immunopathol. 2019 May;41(3):283-297. (PMID: 30891627)

82300872 The China National Natural Science Foundation supported this project; 81970597 The China National Natural Science Foundation supported this project

Keywords: 17+Treg; Chronic prostatitis/chronic pelvic pain syndrome; IL-1β; NLRP3; STAT3

0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (Interleukin-1beta)
0 (STAT3 Transcription Factor)
0 (Nlrp3 protein, mouse)
0 (Inflammasomes)
0 (IL1B protein, mouse)

Date Created: 20240813 Date Completed: 20240813 Latest Revision: 20240816

20240816

PMC11322183

10.1038/s41598-024-69512-2

39138267