Vitamin D regulates immunoglobulin mucin domain molecule‐4 expression in dendritic cells

Liu, Zhiqiang; Li, Mao-Gang; Geng, Xinyu; Li, Jun; Yang, Gui; Qiu, Shuqi; Liu, Zhigang; Yang, Ping‐Chang

doi:10.1111/cea.12894

Cited by 6 publications

(5 citation statements)

References 35 publications

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“…However, blocking the interaction between Tim-4 and Tim-1 with antibodies inhibited the allergic reaction, indicating that modulating Tim-4 function may prove to be an efficient treatment for DC-induced peanut allergy in the future (12). In allergic rhinitis patients, VitD deficiency may contribute to the pathogenesis by increasing the Tim-4 expression on DCs (18).…”

Section: Allergymentioning

confidence: 99%

“…It is reported that probiotics such as Bifidobacterium infantis reduced Tim-4 expression in DCs by inhibiting its transcription factor, STAT6 (17). Vitamin D (VitD) might repress the Tim-4 gene transcription and expression via VitD receptor (18). In addition to expression in immune cells, Tim-4 was also found to be ectopically expressed in tumor cells, including lung cancer (19), colorectal cancer (20), juvenile xanthogranuloma, tissue sarcomas, Langerhans cell sarcoma, and parapharyngeal liposarcoma (21).…”

Section: Introduction To Tim-4mentioning

confidence: 99%

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Tim-4 in Health and Disease: Friend or Foe?

Liang

et al. 2020

Front. Immunol.

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T-cell immunoglobulin and mucin domain containing 4 (Tim-4) is a phosphatidylserine receptor and is selectively expressed on antigen presenting cells. Recently, Tim-4 was reported to be expressed on iNKT cells, B1 cells, and tumor cells, suggesting it has multiple biological functions. In this review, we mainly summarize the expression and regulation of Tim-4 in immune cells including T cells, macrophages, dendritic cells, NKT cells, B cells, and mast cells. The expression of Tim-4 in these cells implies that Tim-4 might participate in immune related diseases. Emerging evidence emphasizes a substantial role for Tim-4 in maintaining homeostasis by regulating various immune responses, including viral infection, allergy, autoimmunity, and tumor immunity. Here, we collectively evaluated the role of Tim-4 in health and diseases. This summary will be extremely useful to fully understand the function of Tim-4 in the pathogenesis of immune related diseases, which would provide novel clues for the diagnosis and treatment of diseases.

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Section: Allergymentioning

confidence: 99%

Section: Introduction To Tim-4mentioning

confidence: 99%

Tim-4 in Health and Disease: Friend or Foe?

Liang

et al. 2020

Front. Immunol.

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“…Previous studies confirmed that the specific microenvironment regulates TIM-4 expression. For instance, TIM-4 expression was downregulated in food allergies (40), but its expression was increased in cancer (41), nonalcohol fatty liver disease (42), allergic rhinitis (43), and asthma (19). Additionally, the expression of TIM-4 in macrophages can be stimulated by various factors in the tumor or nonalcohol fatty liver microenvironment (42,44), such as LPS, danger-associated molecular patterns, ConA, and cytokines.…”

Section: Discussionmentioning

confidence: 99%

TIM-4 in macrophages contributes to nasal polyp formation through the TGF-β1–mediated epithelial to mesenchymal transition in nasal epithelial cells

et al. 2022

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Chronic rhinosinusitis with nasal polyps (CRSwNP) is caused by prolonged inflammation of the paranasal sinus mucosa. The epithelial to mesenchymal transition (EMT) is involved in the occurrence and development of CRSwNP. The T-cell immunoglobulin domain and the mucin domain 4 (TIM-4) is closely related to chronic inflammation, but its mechanism in CRSwNP is poorly understood. In our study, we found that TIM-4 was increased in the sinonasal mucosa of CRSwNP patients and, especially, in macrophages. TIM-4 was positively correlated with α-SMA but negatively correlated with E-cadherin in CRS. Moreover, we confirmed that TIM-4 was positively correlated with the clinical parameters of the Lund-Mackay and Lund-Kennedy scores. In the NP mouse model, administration of TIM-4 neutralizing antibody significantly reduced the polypoid lesions and inhibited the EMT process. TIM-4 activation by stimulating with tissue extracts of CRSwNP led to a significant increase of TGF-β1 expression in macrophages in vitro. Furthermore, coculture of macrophages and human nasal epithelial cells (hNECs) results suggested that the overexpression of TIM-4 in macrophages made a contribution to the EMT process in hNECs. Mechanistically, TIM-4 upregulated TGF-β1 expression in macrophages via the ROS/p38 MAPK/Egr-1 pathway. In conclusion, TIM-4 contributes to the EMT process and aggravates the development of CRSwNP by facilitating the production of TGF-β1 in macrophages. Inhibition of TIM-4 expression suppresses nasal polyp formation, which might provide a new therapeutic approach for CRSwNP.

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“…Another NR, RORα has similar attributes and it exacerbates both asthma and associated comorbidities ( 230 – 235 ). On the other hand, NRs like VDR and Nurr77 seem to be promising in their action and allay asthma, rhinitis, obesity, infection, stress or other co-existing conditions ( 236 – 245 ). Although Nurr77 is a desirable target but is considerably less explored and requires more translational studies.…”

Section: Expert Opinion: Scientific Challenges and Future Perspectivementioning

confidence: 99%

Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment

Tiwari

Gupta

2021

Front. Immunol.

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The escalation in living standards and adoption of ‘Western lifestyle’ has an allied effect on the increased allergy and asthma burden in both developed and developing countries. Current scientific reports bespeak an association between allergic diseases and metabolic dysfunction; hinting toward the critical requirement of organized lifestyle and dietary habits. The ubiquitous nuclear receptors (NRs) translate metabolic stimuli into gene regulatory signals, integrating diet inflences to overall developmental and physiological processes. As a consequence of such promising attributes, nuclear receptors have historically been at the cutting edge of pharmacy world. This review discusses the recent findings that feature the cardinal importance of nuclear receptors and how they can be instrumental in modulating current asthma pharmacology. Further, it highlights a possible future employment of therapy involving dietary supplements and synthetic ligands that would engage NRs and aid in eliminating both asthma and linked comorbidities. Therefore, uncovering new and evolving roles through analysis of genomic changes would represent a feasible approach in both prevention and alleviation of asthma.

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Vitamin D regulates immunoglobulin mucin domain molecule‐4 expression in dendritic cells

Abstract: VitD deficiency may contribute to the pathogenesis of AR by increasing the TIM4 expression. The results suggest that to regulate the serum calcitriol levels and the expression of VDR in DCs may be necessary to be taken into account in the treatment of AR.

Cited by 6 publications

References 35 publications

Tim-4 in Health and Disease: Friend or Foe?

Tim-4 in Health and Disease: Friend or Foe?

TIM-4 in macrophages contributes to nasal polyp formation through the TGF-β1–mediated epithelial to mesenchymal transition in nasal epithelial cells

Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment

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