BCL11B is positioned upstream of PLZF and RORγt to control thymic development of mucosal-associated invariant T cells and MAIT17 program

Drashansky, Theodore T.; Helm, Eric Y.; Curkovic, Nina; Cooper, Jaimee; Cheng, Pingyan; Chen, Xianghong; Gautam, Namrata; Meng, Lingsong; Kwiatkowski, Alexander J.; Collins, William O.; Keselowsky, Benjamin G.; Sant’Angelo, Derek B.; Huo, Zhiguang; Zhang, Weizhou; Zhou, Liang; Avram, Dorina

doi:10.1016/j.isci.2021.102307

Cited by 17 publications

(15 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MiRNAs may participate in the transition from stage 1 to 2, because in the absence of miR-181a/b-1, thymic MAIT cells show low expressions of ROR gt and T -bet (23). The maturation from stage 2 to stage 3 and acquisition of effector function are PLZF dependent, and commensal bacteria along with IL-18 play an important role in the process (17) MAIT17 cells differentiation (25)(26)(27). Recently, MAIT2 cells that express PLZF have been defined using single-cell RNA sequencing analysis, which are considered as developmental intermediates of MAIT1 and MAIT17 cells (28).…”

Section: Distribution and Development Of Mait Cellsmentioning

confidence: 99%

Emerging Roles of Mucosal-Associated Invariant T Cells in Rheumatology

Wei

2022

Front. Immunol.

View full text Add to dashboard Cite

Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset expressing a semi-invariant TCR and recognize microbial riboflavin metabolites presented by major histocompatibility complex class 1-related molecule (MR1). MAIT cells serve as innate-like T cells bridging innate and adaptive immunity, which have attracted increasing attention in recent years. The involvement of MAIT cells has been described in various infections, autoimmune diseases and malignancies. In this review, we first briefly introduce the biology of MAIT cells, and then summarize their roles in rheumatic diseases including systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren’s syndrome, psoriatic arthritis, systemic sclerosis, vasculitis and dermatomyositis. An increased knowledge of MAIT cells will inform the development of novel biomarkers and therapeutic approaches in rheumatology.

show abstract

Section: Distribution and Development Of Mait Cellsmentioning

confidence: 99%

Emerging Roles of Mucosal-Associated Invariant T Cells in Rheumatology

Wei

2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…The innate-like unconventional CD8a + CD8b -TCRab + T cells, which are NK1.1 + in mice or CD161 + in humans, are abundantly present in livers, exhibit an activated/memory phenotype, and use a perforin-dependent mechanism to dampen autoimmune responses in vivo (58). Not unexpectedly, the development of these MAIT and unconventional CD8a + CD8b -TCRab + T cells are highly, albeit not absolutely, dependent on ZBTB16 as well (57)(58)(59)(60).…”

Section: Zbtb16 (Plzf)mentioning

confidence: 99%

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

Cheng

Gao

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

The development and differentiation of T cells represents a long and highly coordinated, yet flexible at some points, pathway, along which the sequential and dynamic expressions of different transcriptional factors play prominent roles at multiple steps. The large ZBTB family comprises a diverse group of transcriptional factors, and many of them have emerged as critical factors that regulate the lineage commitment, differentiation and effector function of hematopoietic-derived cells as well as a variety of other developmental events. Within the T-cell lineage, several ZBTB proteins, including ZBTB1, ZBTB17, ZBTB7B (THPOK) and BCL6 (ZBTB27), mainly regulate the development and/or differentiation of conventional CD4/CD8 αβ+ T cells, whereas ZBTB16 (PLZF) is essential for the development and function of innate-like unconventional γδ+ T & invariant NKT cells. Given the critical role of T cells in host defenses against infections/tumors and in the pathogenesis of many inflammatory disorders, we herein summarize the roles of fourteen ZBTB family members in the development, differentiation and effector function of both conventional and unconventional T cells as well as the underlying molecular mechanisms.

show abstract

“…The T cells that accumulated in Bcl11b ΔiThy mice did not express PLZF, which is a Bcl11b-dependent transcription factor characteristic of MAIT cells and iNKT cells (Supplementary Fig. 2e ) 14 , confirming that they are not MAIT cells. Thus, the expansion of non-canonical MR1-reactive αβ T cells is associated with the development of chronic inflammation in Bcl11b ΔiThy mice.…”

Section: Resultsmentioning

confidence: 76%

Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b

et al. 2022

View full text Add to dashboard Cite

MHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b∆iThy mice) develop chronic inflammation. Bcl11b∆iThy mice lack conventional T cells and MAIT cells, whereas CD4+IL-18R+ αβ T cells expressing skewed Traj33 (Jα33)+ T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33+ T cells expanded in Bcl11b∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential.

show abstract

BCL11B is positioned upstream of PLZF and RORγt to control thymic development of mucosal-associated invariant T cells and MAIT17 program

Cited by 17 publications

References 70 publications

Emerging Roles of Mucosal-Associated Invariant T Cells in Rheumatology

Emerging Roles of Mucosal-Associated Invariant T Cells in Rheumatology

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b

Contact Info

Product

Resources

About