Hobit identifies tissue-resident memory T cell precursors that are regulated by Eomes

Parga-Vidal, Loreto; Behr, Felix M.; Kragten, Natasja A. M.; Nota, Benjamin; Wesselink, Thomas H.; Kavazović, Inga; Covill, Laura; Schuller, Margo B.P.; Bryceson, Yenan T.; Wensveen, Felix M.; Lier, René A. W. van; Dam, Teunis J. P. van; Stark, Regina; Gisbergen, Klaas P.J.M. van

doi:10.1126/sciimmunol.abg3533

Cited by 68 publications

(60 citation statements)

References 75 publications

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“…In T cells, Eomes suppresses the formation of T RM precursors and T RM through Hobit downregulation, acting as a key TF for the regulation of lineage choice between circulating and resident memory T cells. [54] In contrast, T-bet overexpression results in increased expression levels of Hobit compared with controls. Therefore, Hobit is negatively and positively regulated by Eomes and T-bet in CD8 + T cells, respectively.…”

Section: Control Of Tissue Residency Versus Traffickingmentioning

confidence: 98%

“…Therefore, Hobit is negatively and positively regulated by Eomes and T-bet in CD8 + T cells, respectively. [54] Moreover, T-bet and Eomes ChIP-seq experiments identified peaks at the Hobit locus suggesting that this regulation was a direct activity of Eomes and T-bet [54,55] . Similar binding peaks at Hobit locus were also identified in NK cells.…”

Section: Control Of Tissue Residency Versus Traffickingmentioning

confidence: 99%

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Eomes and T‐bet, a dynamic duo regulating NK cell differentiation

2022

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T-bet and Eomes are two related transcription factors (TFs) that regulate the differentiation of cytotoxic lymphocytes such as Natural Killer (NK) cells and CD8 T cells.Recent genome-wide analyses suggest they have complementary roles in instructing the transcriptional program of NK cells, although their DNA binding sites appear to be very similar. In this essay, we discuss the mechanisms that could specify their action, addressing their expression profile, the cofactors they interact with, as well as their roles in the epigenetic regulation of chromatin accessibility. Based on the recent literature on these TFs, we propose different models to describe how they regulate gene expression in NK cells at steady state, or in the context of activation or exhaustion.We also discuss recent findings in the field of CD8 T cell differentiation and residency, where Eomes and T-bet appear to be major regulators, and the parallels that can be drawn between mechanisms of NK and CD8 T cell differentiation and trafficking. K E Y W O R D S cytotoxicity, development, IFN-γ, natural Killer cells, T-box transcription factors NK CELL DIFFERENTIATION, PARALLELS WITH T CELLSNK cells develop mainly in the bone marrow (BM). At early developmental stages, they actively proliferate in this anatomical site before maturation. We previously reported that immature NK cells could be dissected into two different subsets expressing or not CD27. [10] However, mathematical modeling led us to refine this model and propose that most immature NK cells were in fact CD11b − CD27 + . [11]

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Section: Control Of Tissue Residency Versus Traffickingmentioning

confidence: 98%

Section: Control Of Tissue Residency Versus Traffickingmentioning

confidence: 99%

Eomes and T‐bet, a dynamic duo regulating NK cell differentiation

2022

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“…However, how and when Hobit and Blimp-1 instruct the branching off of Trm from terminal effectors and circulating memory T cells upon infection remains unresolved. Expression of Hobit appears highly restricted to the Trm lineage and allows for the unequivocal identification of Trm precursors [17,22]. In contrast, Blimp-1 is broadly expressed in antigen-experienced T cells and promotes terminal differentiation of effector CD8 + T cells besides instructing Trm formation [8,9,22].…”

Section: Introductionmentioning

confidence: 99%

Hobit and Blimp‐1 regulate T_RM abundance after LCMV infection by suppressing tissue exit pathways of T_RMprecursors

et al. 2022

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Tissue-resident memory T cells (Trm) are retained in peripheral tissues after infection for enhanced protection against secondary encounter with the same pathogen. We have previously shown that the transcription factor Hobit and its homolog Blimp-1 drive Trm development after viral infection, but how and when these transcription factors mediate Trm formation remains poorly understood. In particular, the major impact of Blimp-1 in regulating several aspects of effector T-cell differentiation impairs study of its specific role in Trm development. Here, we used the restricted expression of Hobit in the Trm lineage to develop mice with a conditional deletion of Blimp-1 in Trm, allowing us to specifically investigate the role of both transcription factors in Trm differentiation. We found that Hobit and Blimp-1 were required for the upregulation of CD69 and suppression of CCR7 and S1PR1 on virus-specific Trm precursors after LCMV infection, underlining a role in their retention within tissues. The early impact of Hobit and Blimp-1 favored Trm formation and prevented the development of circulating memory T cells. Thus, our findings highlight a role of Hobit and Blimp-1 at the branching point of circulating and resident memory lineages by suppressing tissue egress of Trm precursors early during infection.

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“…Runx3 plays a primary role in CD8 + T RM differentiation by enhancing the expression of core residency signature and repressing the expression of signature genes of T CM ( 30 , 31 ). Downregulation of T-box transcription factor Eomes and T-bet is also necessary for early-stage T RM differentiation ( 32 , 33 ). Recent studies have found that effector-like and memory-like CD8 + T RM subsets can be distinguished by differential expression of two transcriptional factors Blimp-1 and Id3.…”

Section: T Rm In the Intestinementioning

confidence: 99%

An Overview of Tissue-Resident Memory T Cells in the Intestine: From Physiological Functions to Pathological Mechanisms

2022

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The human intestine contains a complex network of innate and adaptive immune cells that provide protective immunity. The dysfunction of this network may cause various chronic diseases. A large number of T cells in the human intestine have been identified as tissue-resident memory T cells (TRM). TRM are present in the peripheral tissues, and they do not recirculate through the blood. It is known that TRM provide rapid immune responses at the frontline of pathogen invasion. Recent evidence also suggests that these cells play a role in tumor surveillance and the pathogenesis of autoimmune diseases. In this review, we discuss the general features of intestinal TRM together with their role in intestinal infection, colorectal cancer (CRC), and inflammatory bowel disease (IBD).

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Hobit identifies tissue-resident memory T cell precursors that are regulated by Eomes

Abstract: Hobit-expressing effector CD8 + T cells are T RM precursors, whose formation is regulated by the T-box transcription factor Eomes.

Cited by 68 publications

References 75 publications

Eomes and T‐bet, a dynamic duo regulating NK cell differentiation

Eomes and T‐bet, a dynamic duo regulating NK cell differentiation

Hobit and Blimp‐1 regulate T_RM abundance after LCMV infection by suppressing tissue exit pathways of T_RMprecursors

An Overview of Tissue-Resident Memory T Cells in the Intestine: From Physiological Functions to Pathological Mechanisms

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Hobit identifies tissue-resident memory T cell precursors that are regulated by Eomes

Abstract: Hobit-expressing effector CD8 + T cells are T RM precursors, whose formation is regulated by the T-box transcription factor Eomes.

Cited by 68 publications

References 75 publications

Eomes and T‐bet, a dynamic duo regulating NK cell differentiation

Eomes and T‐bet, a dynamic duo regulating NK cell differentiation

Hobit and Blimp‐1 regulate TRM abundance after LCMV infection by suppressing tissue exit pathways of TRMprecursors

An Overview of Tissue-Resident Memory T Cells in the Intestine: From Physiological Functions to Pathological Mechanisms

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Hobit and Blimp‐1 regulate T_RM abundance after LCMV infection by suppressing tissue exit pathways of T_RMprecursors