Minghua Feng

Shanghai Jiao Tong University

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Guoyao Tang

Shanghai Jiao Tong University

Yirao Lai

Shanghai Ninth People's Hospital

Yufeng Wang

Peking University

Lei Pan

Shanghai Ninth People's Hospital

Yiwen Deng

Shanghai Ninth People's Hospital

Xiaozhe Han

Nova Southeastern University

Xinke Jiang

Shanghai Jiao Tong University

Lei Sun

Beijing Ditan Hospital

Jin Li

Fudan University

Xi-ye Li

Shanghai Ninth People's Hospital

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Shanghai Ninth People's Hospital

Shanghai Jiao Tong University

Fudan University

National Clinical Research Center for Digestive Diseases

Chinese Academy of Medical Sciences & Peking Union Medical College

National Clinical Research

Capital Medical University

Stomatology Hospital

Nova Southeastern University

Sun Yat-sen University

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Author response for "<scp>CCL19</scp>+ Fibroblasts Promote Tertiary Lymphoid Structure in Oral Lichen Planus: A Retrospective Study"

Yirao Lai Lei Pan Xinke Jiang Yiwen Deng Ming‐Hua Feng

10.1111/odi.15266/v4/response1

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Author response for "<scp>CCL19</scp>+ Fibroblasts Promote Tertiary Lymphoid Structure in Oral Lichen Planus: A Retrospective Study"

Yirao Lai Lei Pan Xin‐Ke Jiang Yiwen Deng Ming‐Hua Feng

10.1111/odi.15266/v2/response1

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Characterizing inducible tertiary lymphoid structures in oral lichen planus: implications for stromal-immune cells interaction and disease severity

Research Square (Research Square) (2024)

Guoyao Tang Yirao Lai Lei Pan Xinke Jiang Yiwen Deng

Abstract Stromal-immune cells interaction and their contribution in the pathogenesis of oral mucositis, remained not fully understood. This made it hard to clarify the underlying mechanism linking systemic immunity and regional immune microenvironment. The present study aims to elucidate the underpinnings of oral lichen planus (OLP) by focusing on the role of inducible tertiary lymphoid structures (iTLSs) and their impact on disease progression. Employing single-cell RNA sequencing and multiple immunofluorescences, we identified distinct cellular compositions and stromal-immune cells interactions within the iTLSs of OLP. We particularly highlighted the role of CCL19⁺ fibroblasts and HEV cells. These stromal cells might play a crucial role in facilitating lymphocytes trafficking from peripheral blood to the local inflammation sites within oral mucosa, thereby promoting the formation of iTLSs in OLP. Our findings also revealed a significant correlation between the presence of iTLSs and increased severity of OLP, marked by more atrophic-erosive forms and higher REU scores in patients with iTLSs. The present research offered new insights into the pathogenic mechanisms of OLP, proposing the stromal-immune cell interactions within iTLSs as essential factors in the disease's inflammatory milieu. These findings contributed to uncovering the specific regional pathological features in OLP. Hence, the characterization of iTLSs provided a fundamental foundation for further studies in oral mucosal immunity.

Oral Lichen Planus

10.21203/rs.3.rs-4017711/v1

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B cells infiltration potentially responded better to systemic corticoids in oral lichen planus and oral lichenoid lesions

Research Square (Research Square) (2024)

Ming‐Hua Feng Yirao Lai Yiwen Deng Xi-ye Li Lei Pan

Abstract Background: Oral lichen planus (OLP) and oral lichenoid lesion (OLL) are common chronic inflammation in the oral mucosa. B cells infiltration in OLP and OLL, however, little is known about these cells in OLP and OLL. Objectives: To analyze the function and infiltrating features of B lymphocytes in OLP and OLL, and to preliminarily evaluate their correlation with clinical outcomes. Methods: Tissue samples were collected from OLP, OLL, and healthy mucosa. The phenotypes and amounts of B cells in tissues were analyzed by single-cell sequencing. Their proportion and infiltrating features in tissues were examined by immunohistochemistry and immunofluorescence. With the systemic medication of corticoids, the correlation between B cells infiltrating characteristics and the clinical outcomes were evaluated. Results: A quantified proportion increase of B cells was shown in both OLP and OLL. B cells in OLP demonstrated heightened activation and enhanced regulation in immune response. A cohort of 100 patients with OLP/OLL and 13 healthy controls were examined to investigate the B cells infiltration pattern. B cells were distributed in the superficial layer of lamina propria in 92.9% and 41.9% of OLP and OLL, respectively(P<0.01); focally distributed in 25.0% and 62.9% of OLP and OLL, respectively(P<0.01). With the systemic medication of corticoids, the cases with B cell infiltration (B⁺) in OLP and OLL groups showed a statistically significant reduction in REU scores before and after treatment (P<0.01) Conclusions: B cells are widely present in OLP and OLL, and B cell infiltration in OLP and OLL are related to the better therapeutic effect of oral corticoids.

Oral Lichen Planus

Lamina propria

Oral mucosa

Infiltration (HVAC)

10.21203/rs.3.rs-4292822/v1

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Group 1 and 3 innate lymphoid cells are increased in oral lichen planus and oral lichenoid lesions

Oral Diseases (2022)

Lei Pan Ming‐Hua Feng Junjun Chen Shu Deng Xiaozhe Han

Innate lymphoid cells (ILCs) are vital innate immune cells cooperating with T cells. While their phenotypes and functions in oral mucosa kept unclear yet. In the present study, the relative proportions and distribution of different ILC subsets in oral mucosa of oral lichen planus (OLP), oral lichenoid lesions (OLL), and controls were compared.Oral mucosal samples were collected from control (n = 29), OLP (n = 20), and OLL (n = 22) donors. ILCs subsets were characterized in single-cell suspensions by flow cytometry. Immunohistochemistry was performed to locate the CD127+ cells in situ.ILCs were present in healthy and increased infiltration in OLP/OLL (p = 0.0092, p = 0.0216). Infiltration of ILC1 increased in OLP/OLL mucosa (p = 0.0225, p = 0.0399), as did the infiltration of ILC3 increase in OLL mucosa (p = 0.0128). The ILC2/ILCs ratio was significantly reduced in OLP and OLL (p = 0.0124, p = 0.0346). CD127+ cells were mainly located closely at the basement membrane.The results of increased ILC1, decreased ILC2, and increased ILC3 suggested that changes of ILC distributions in oral mucosa may be relevant to persistent inflammation in local tissues, by promoting immune factors and weakening repair capacity.

Oral Lichen Planus

Innate lymphoid cell

Oral mucosa

Infiltration (HVAC)

Interleukin-7 receptor

10.1111/odi.14384

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B Cells Infiltration Potentially Responded Better to Systemic Corticoids in Oral Lichen Planus and Oral Lichenoid Lesions

Inflammation (2024)

Ming‐Hua Feng Yirao Lai Yiwen Deng Xi-ye Li Lei Pan

Oral Lichen Planus

Lamina propria

Oral mucosa

Infiltration (HVAC)

10.1007/s10753-024-02112-4

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TRIM21 promotes inflammation by ubiquitylating NF‐κB in T cells of oral lichen planus

Journal of Oral Pathology and Medicine (2023)

Yilin Yao Lei Pan Wei Ye Ming‐Hua Feng Xiye Li

Oral lichen planus (OLP) is a mucocutaneous inflammatory disease affecting 1% general population. Tripartite motif-containing protein 21 (TRIM21) shows a significant role in OLP. This study aimed to explore the function and mechanism of TRIM21 in T cells of OLP.Differential gene expression profile in OLP versus healthy controls (HCs) was constructed by RNA sequencing. Protein expression level and infiltration sites of TRIM21 in OLP were detected by immunoblot, immunohistochemistry, and immunofluorescence. Expression of proinflammatory cytokines and chemokines including IL-6, TNF-α, ICAM1, CXCL1, CXCL8, CXCL9, and CXCL11 in CD3+ TRIM21hi T cells were measured by quantitative real-time polymerase chain reaction analysis. Downstream pathways and substrates of TRIM21 were explored by immunoblot and immunoprecipitation. Whether TRIM21 ubiquitination its substrate and ubiquitination form were tested by ubiquitination assay in vitro.Compared with HCs, TRIM21 exhibited a higher level in OLP, which expressed mainly in CD3+ T lymphocytes in OLP tissues. Overexpressed TRIM21 enhanced the expression of IL-6, TNF-α, CXCL1, CXCL8, CXCL9, and CXCL11 in CD3+ T cell line through ubiquitinating nuclear factor-κB (NF-κB) via a lysine 63 (K63) linkage, which eventually activating NF-κB signaling pathway.In OLP, TRIM21 promoted inflammation through ubiquitylating NF-κB and activating NF-κB signaling pathway.

Proinflammatory cytokine

CXCL1

Oral Lichen Planus

CXCL9

CXCL2

10.1111/jop.13428

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CCL19⁺ Fibroblasts Promote Tertiary Lymphoid Structure in Oral Lichen Planus: A Retrospective Study

Oral Diseases (2025)

Yirao Lai Lei Pan Xinke Jiang Yiwen Deng Ming‐Hua Feng

ABSTRACT Objectives The priming mechanism of adaptive immunity in oral mucositis remains unclarified. This study aimed to elucidate the mechanisms of oral lichen planus (OLP), with a specific focus on the role of inducible tertiary lymphoid structures (iTLSs) and stromal‐immune microenvironments within OLP. Materials and Methods We employed single‐cell RNA sequencing and multiplex immunofluorescence staining to characterize the spatial characteristics and transcriptional signature of iTLSs in OLP. To investigate whether the presence of iTLSs influences the disease severity of OLP, we retrospectively collected clinical data from OLP patients. Results Based on single‐cell resolution analysis, we identified distinct cellular compositions and fibroblast‐immune cells interactions within the iTLSs of OLP. We highlighted the critical role of CCL19 + fibroblasts in T‐cell chemotaxis, promoting the development of iTLSs. Lymphotoxin was demonstrated to activate fibroblasts expressing CCL19. We revealed a significant correlation between the presence of iTLSs and increased severity of OLP, marked by more atrophic‐erosive forms and higher disease scores in patients with iTLSs. Conclusions The present research proposed the fibroblast‐immune cell interactions within iTLSs as essential factors in OLP's inflammatory milieu, indicating iTLSs as the priming structure of T‐cell immunity in the local oral mucosa.

Oral Lichen Planus

CCL19

Oral mucosa

10.1111/odi.15266

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Author response for "<scp>CCL19</scp>+ Fibroblasts Promote Tertiary Lymphoid Structure in Oral Lichen Planus: A Retrospective Study"

Yirao Lai Lei Pan Xinke Jiang Yiwen Deng Ming‐Hua Feng

10.1111/odi.15266/v3/response1

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