SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation

Wu, Xin; Wang, Yun; Huang, Rui; Gai, Qu-Jing; Liu, Haofei; Shi, Min; Zhang, Xiang; Zuo, Yonglin; Chen, Longjuan; Zhao, Qi-Wen; Shi, Yu; Wang, Fengchao; Yan, Xiaowei; Lu, Huiping; Xu, Senlin; Yao, Xiaohong; Chen, Lin; Tian, Qiang; Yang, Ziyan; Zhong, Bo; Dong, Chen; Wang, Yan; Bian, Xiu‐Wu; Liu, Xindong

doi:10.1126/science.aba6652

Cited by 35 publications

(38 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sostdc1 plays many roles in development of tissues (including development of the eye [49]) and in promoting cancer. Recent study using SOSTDC1-reporter mice identified a potential regulatory role for Tfh-secreted SOSTDC1 in promoting the development of regulatory follicular T cells in germinal centers following viral infection or immunization [50]. Notably, these SOSTDC1-secreting Tfh cells expressed lower levels of Il21 and lost the ability to help B cells.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice

Debreceni

Chimenti

Serreze

et al. 2020

IJMS

View full text Add to dashboard Cite

Sjögren syndrome (SS) is an immunologically complex, chronic autoimmune disease targeting lacrimal and salivary glands. Nonobese diabetic (NOD) mice spontaneously develop inflammation of lacrimal and salivary glands with histopathological features similar to SS in humans including focal lymphocytic infiltrates in the affected glands. The innate immune signals driving lymphocytic infiltration of these glands are not well-defined. Here we evaluate the role of Toll-like receptor (TLR) 7 in the development of SS-like manifestations in NOD mice. We created a Tlr7 knockout NOD mouse strain and performed histological and gene expression studies to characterize the effects of TLR7 on autoimmunity development. TLR7 was required for male-specific lacrimal gland inflammation but not for female-specific salivary gland inflammation. Moreover, TLR7 was required for type 1 diabetes development in male but not female NOD mice. RNA sequencing demonstrated that TLR7 was associated with a type I interferon (IFN) response and a type I IFN-independent B cell response in the lacrimal glands. Together these studies identify a previously unappreciated pathogenic role for TLR7 in lacrimal gland autoimmunity and T1D development in male NOD mice adding to the growing body of evidence supporting sex differences in mechanisms of autoimmune disease in NOD mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice

Debreceni

Chimenti

Serreze

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…The tumor necrosis factor receptor-associated factor 3 signaling maintains a high ICOS expression in Treg cells, and a high ICOS level is required for Tfr cell generation [64]. Moreover, in mice, sclerostin domaincontaining protein 1, secreted by a Tfh cell subpopulation, facilitates Tfr cell differentiation by blocking the Wnt/β-catenin axis, upregulating Foxp3, CXCR5, and CTLA-4 expression [65] (Fig. 2).…”

Section: Transcription Factorsmentioning

confidence: 99%

Differentiation, functions, and roles of T follicular regulatory cells in autoimmune diseases

Nakayamada

Tanaka

2021

Inflamm Regener

View full text Add to dashboard Cite

T follicular helper cells participate in stimulating germinal center (GC) formation and supporting B cell differentiation and autoantibody production. However, T follicular regulatory (Tfr) cells suppress B cell activation. Since changes in the number and functions of Tfr cells lead to dysregulated GC reaction and autoantibody response, targeting Tfr cells may benefit the treatment of autoimmune diseases. Differentiation of Tfr cells is a multistage and multifactorial process with various positive and negative regulators. Therefore, understanding the signals regulating Tfr cell generation is crucial for the development of targeted therapies. In this review, we discuss recent studies that have elucidated the roles of Tfr cells in autoimmune diseases and investigated the modulators of Tfr cell differentiation. Additionally, potential immunotherapies targeting Tfr cells are highlighted.

show abstract

“…Recent evidence indicates that Tfh cells can convert into Tfr cells in an IL-2 dependent manner, providing new insights into regulation of Tfr/ Tfh balance (107). Moreover, in a breakthrough discovery, Wu et al (108) found a distinct subset of Tfh cells that could promote Tfr cell differentiation by blocking the Wnt-b-catenin axis in a sclerostin domain-containing protein 1-dependent (SOSTDC-1) manner. Elucidating the cellular and molecular mechanisms underlying the activities of Tfh and Tfr cells in the GC response as well as predominant determinants of the Tfr/Tfh balance will contribute to the regulation of autoantibody production.…”

Section: Involvement Of Tfh and Tfr In Autoimmune Diseases Tfh And Tfr Control Autoantibody Productionmentioning

confidence: 99%

Frontiers of Autoantibodies in Autoimmune Disorders: Crosstalk Between Tfh/Tfr and Regulatory B Cells

Ding

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Balance of Tfh/Tfr cell is critically important for the maintenance of immune tolerance, as evidenced by the fact that T follicular helper (Tfh) cells are central to the autoantibodies generation through providing necessary help for germinal center (GC) B cells, whereas T follicular regulatory (Tfr) cells significantly inhibit autoimmune inflammation process through restraining Tfh cell responses. However, signals underlying the regulation of Tfh and Tfr cells are largely undefined. Regulatory B cells (Bregs) is a heterogeneous subpopulation of B cells with immunosuppressive function. Considerable advances have been made in their functions to produce anti‐inflammatory cytokines and to regulate Th17, Th1, and Treg cells in autoimmune diseases. The recent identification of their correlations with dysregulated Tfr/Tfh cells and autoantibody production makes Bregs an important checkpoint in GC response. Bregs exert profound impacts on the differentiation, function, and distribution of Tfh and Tfr cells in the immune microenvironment. Thus, unraveling mechanistic information on Tfh-Breg and Tfr-Breg interactions will inspire novel implications for the establishment of homeostasis and prevention of autoantibodies in diverse diseases. This review summarizes the dysregulation of Tfh/Tfr cells in autoimmune diseases with a focus on the emerging role of Bregs in regulating the balance between Tfh and Tfr cells. The previously unsuspected crosstalk between Bregs and Tfh/Tfr cells will be beneficial to understand the cellular mechanisms of autoantibody production and evoke a revolution in immunotherapy for autoimmune diseases.

show abstract

SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation

Cited by 35 publications

References 35 publications

Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice

Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice

Differentiation, functions, and roles of T follicular regulatory cells in autoimmune diseases

Frontiers of Autoantibodies in Autoimmune Disorders: Crosstalk Between Tfh/Tfr and Regulatory B Cells

Contact Info

Product

Resources

About