Biological functions and clinical implications of interleukin-34 in inflammatory diseases

Ge, Yun; Huang, Man; Zhu, Xiaomei; Yao, Yong‐Ming

doi:10.1016/bs.apcsb.2019.02.003

Cited by 7 publications

(4 citation statements)

References 118 publications

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“…A variety of cells, such as immune cells, epithelial cells, and stromal cells, can express IL-34 [27]. In our study, we detected the location of IL-34 in the uteri by IHC staining, and found that IL-34 was predominantly colocalized to the glandular and luminal epithelial cells, with additional immunostaining in endometrial stromal cells (Supporting Information Fig.…”

Section: Discussionmentioning

confidence: 52%

Interleukin‐34 accelerates intrauterine adhesions progress related to CX3CR1⁺ monocytes/macrophages

Wang

Pan

et al. 2021

Eur J Immunol

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Intrauterine adhesions (IUA) are characterized by endometrial fibrosis and impose a great challenge for female reproduction. IL-34 is profoundly involved in various fibrotic diseases through regulating the survival, proliferation, and differentiation of monocytes/macrophages. However, it remains unclear how IL-34 regulates monocytes/macrophages in context of IUA. Here, we showed that the expression level of IL-34 and the amount of CX3CR1+ monocytes/macrophages were significantly increased in endometrial tissues of IUA patients. IL-34 promoted the differentiation of monocytes/macrophages, which express CX3CR1 via CSF-1R/P13K/Akt pathway in vitro. Moreover, IL-34-induced CX3CR1+ monocytes/macrophages promoted the differentiation of endometrial stromal cells into myofibroblasts. Of note, IL-34 caused endometrial fibrosis and increased the amount of CX3CR1+ monocytes/macrophages in endometrial tissues in vivo. IL-34 modulated endometrial fibrosis by regulating monocytes/macrophages since the elimination of endometrial monocytes/macrophages significantly suppressed the profibrotic function of IL-34. Finally, blocking of IL-34 in the LPS-IUA model resulted in the improvement of endometrial fibrosis and decreased number of CX3CR1+ monocytes/macrophages. Our studies uncover the novel mechanism of interaction between IL-34-induced CX3CR1+ monocytes/macrophages and endometrial stromal cells in endometrial fibrosis pathogenesis, and highlight IL-34 as a critical target for treating IUA.

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Section: Discussionmentioning

confidence: 52%

Interleukin‐34 accelerates intrauterine adhesions progress related to CX3CR1⁺ monocytes/macrophages

Wang

Pan

et al. 2021

Eur J Immunol

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“…Furthermore, glycation end products stimulate the production of proinflammatory proteins by interacting with specific receptors in the serum and gingival tissues of patients with diabetes, resulting in tissue damage [ 32 ]. IL-34-associated inflammation plays a critical role in various metabolic diseases [ 33 ]. Previous studies have reported an association between increased IL-34 levels and insulin resistance in obese patients [ 8 33 34 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…IL-34-associated inflammation plays a critical role in various metabolic diseases [ 33 ]. Previous studies have reported an association between increased IL-34 levels and insulin resistance in obese patients [ 8 33 34 35 ]. In a study by Guruprasad and Pradeep [ 31 ], 175 individuals who were PH or had gingivitis or periodontitis were evaluated.…”

Section: Discussionmentioning

confidence: 99%

Gingival crevicular fluid CSF-1 and IL-34 levels in patients with stage III grade C periodontitis and uncontrolled type 2 diabetes mellitus

Dikilitaş

Karaaslan

Evirgen

et al. 2022

J Periodontal Implant Sci

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Purpose Periodontal diseases are inflammatory conditions that alter the host’s response to microbial pathogens. Type 2 diabetes mellitus (T2DM) is a complex disease that affects the incidence and severity of periodontal diseases. This study investigated the gingival crevicular fluid (GCF) levels of colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34) in patients with stage III grade C periodontitis (SIII-GC-P) and stage III grade C periodontitis with uncontrolled type 2 diabetes (SIII-GC-PD). Methods In total, 72 individuals, including 24 periodontally healthy (PH), 24 SIII-GC-P, and 24 SIII-GC-PD patients, were recruited for this study. Periodontitis patients (stage III) had interdental attachment loss (AL) of 5 mm or more, probing depth (PD) of 6 mm or more, radiographic bone loss advancing to the middle or apical part of the root, and tooth loss (<5) due to periodontal disease. Radiographic bone loss in the teeth was also evaluated; grade C periodontitis was defined as a ratio of the percentage of root bone loss to age greater than 1.0. The plaque index (PI), gingival index (GI), presence of bleeding on probing (BOP), PD, and clinical AL were used for clinical periodontal assessments. GCF samples were obtained and analyzed using an enzyme-linked immunosorbent assay. Results All clinical parameters—PD, AL, GI, BOP, and PI—were significantly higher in the SIII-GC-PD group than in the PH and SIII-GC-P groups for both the full mouth and each sampling site ( P <0.05). The total IL-34 and CSF-1 levels were significantly higher in the SIII-GC-PD group than in the PH and SIII-GC-P groups ( P <0.05), and there were significant differences between the periodontitis groups ( P <0.05). Conclusions These findings suggest that IL-34 and CSF-1 expression increases in patients with SIII-GC-PD. CSF-1 was associated with the inflammatory status of periodontal tissues and T2DM, while IL-34 was associated only with T2DM. Trial Registration ClinicalTrials.gov Identifier: NCT04891627

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“…As a novel cytokine identified in 2008, IL-34 is testified as monocytes and macrophages-specific CSF-1R ligand, and the interaction results in CSF-1R specific tyrosine residues autophosphorylation, which may lead to adaptor proteins and kinases recruitment to activate STAT3, ERK1/2, and NF-κB pathway ( 22 24 ). Such activation may promote IL-34-mediated differentiation and viability of monocytes and macrophages ( 25 26 27 ).…”

Section: Discussionmentioning

confidence: 99%

IL-34 Aggravates Steroid-Induced Osteonecrosis of the Femoral Head via Promoting Osteoclast Differentiation

et al. 2022

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IL-34 can promote osteoclast differentiation and activation, which may contribute to steroid-induced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.

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Biological functions and clinical implications of interleukin-34 in inflammatory diseases

Cited by 7 publications

References 118 publications

Interleukin‐34 accelerates intrauterine adhesions progress related to CX3CR1⁺ monocytes/macrophages

Interleukin‐34 accelerates intrauterine adhesions progress related to CX3CR1⁺ monocytes/macrophages

Gingival crevicular fluid CSF-1 and IL-34 levels in patients with stage III grade C periodontitis and uncontrolled type 2 diabetes mellitus

IL-34 Aggravates Steroid-Induced Osteonecrosis of the Femoral Head via Promoting Osteoclast Differentiation

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Biological functions and clinical implications of interleukin-34 in inflammatory diseases

Cited by 7 publications

References 118 publications

Interleukin‐34 accelerates intrauterine adhesions progress related to CX3CR1+ monocytes/macrophages

Interleukin‐34 accelerates intrauterine adhesions progress related to CX3CR1+ monocytes/macrophages

Gingival crevicular fluid CSF-1 and IL-34 levels in patients with stage III grade C periodontitis and uncontrolled type 2 diabetes mellitus

IL-34 Aggravates Steroid-Induced Osteonecrosis of the Femoral Head via Promoting Osteoclast Differentiation

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Interleukin‐34 accelerates intrauterine adhesions progress related to CX3CR1⁺ monocytes/macrophages

Interleukin‐34 accelerates intrauterine adhesions progress related to CX3CR1⁺ monocytes/macrophages