T Cell Factor 1 Suppresses CD103+ Lung Tissue-Resident Memory T Cell Development

Wu, Jingxia; Madi, Alaa; Mieg, Alessa; Hotz‐Wagenblatt, Agnes; Weisshaar, Nina; Ma, Shaolin; Möhr, Kerstin; Schlimbach, Tilo; Hering, Marvin; Borgers, Helena; Cui, Guoliang

doi:10.1016/j.celrep.2020.03.048

Cited by 47 publications

(35 citation statements)

References 55 publications

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“…Similar reciprocal regulation was also observed between TGF-β and another T-box transcription factor Eomesodermin (Eomes) [ 85 ]. T cell factor 1 (TCF1) can also directly bind to Itgae gene locus to suppress CD103 expression and CD103 + CD8 T RM cell formation [ 86 ]. Interestingly, TGF-β can inhibit TCF1 protein expression and reduce the recruitment of TCF1 to the Itgae gene locus, which represses the negative regulation of TCF1 on CD103 expression [ 86 ].…”

Section: Mechanisms By Which Tgf-β Regulates the Development And Maintenance Of Cd103 + Cd8 T Rm Cementioning

confidence: 99%

“…T cell factor 1 (TCF1) can also directly bind to Itgae gene locus to suppress CD103 expression and CD103 + CD8 T RM cell formation [ 86 ]. Interestingly, TGF-β can inhibit TCF1 protein expression and reduce the recruitment of TCF1 to the Itgae gene locus, which represses the negative regulation of TCF1 on CD103 expression [ 86 ]. TCF1 is critical for T CM cell differentiation and longevity [ 87 , 88 ].…”

Section: Mechanisms By Which Tgf-β Regulates the Development And Maintenance Of Cd103 + Cd8 T Rm Cementioning

confidence: 99%

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TGF-β: Many Paths to CD103+ CD8 T Cell Residency

Qiu

Chu

Sheridan

2021

Cells

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CD8 tissue-resident memory T (TRM) cells primarily reside in nonlymphoid tissues without recirculating and provide front-line protective immunity against infections and cancers. CD8 TRM cells can be generally divided into CD69+ CD103− TRM cells (referred to as CD103− TRM cells) and CD69+ CD103+ TRM cells (referred to as CD103+ TRM cells). TGF-β plays a critical role in the development and maintenance of CD103+ CD8 TRM cells. In this review, we summarize the current understanding of tissue-specific activation of TGF-β mediated by integrins and how it contributes to CD103+ CD8 TRM cell development and maintenance. Furthermore, we discuss the underlying mechanisms utilized by TGF-β to regulate the development and maintenance of CD103+ CD8 TRM cells. Overall, this review highlights the importance of TGF-β in regulating this unique subset of memory CD8 T cells that may shed light on improving vaccine design to target this population.

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Section: Mechanisms By Which Tgf-β Regulates the Development And Maintenance Of Cd103 + Cd8 T Rm Cementioning

confidence: 99%

Section: Mechanisms By Which Tgf-β Regulates the Development And Maintenance Of Cd103 + Cd8 T Rm Cementioning

confidence: 99%

TGF-β: Many Paths to CD103+ CD8 T Cell Residency

Qiu

Chu

Sheridan

2021

Cells

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“…(Figure 2C-D). Expression of CD103 and differentiation of T RM s are regulated by antigen receptor signaling and expression of transcription factors such as T-bet and TCF-1 (44–46). First, we quantified levels of transcription factors T-bet and TCF-1 in NP366-specific effector CD8 T cells in lungs of vaccinated WT and CCR2 -/- mice.…”

Section: Resultsmentioning

confidence: 99%

CCR2 Regulates Vaccine-Induced Mucosal T-Cell Memory to Influenza A Virus

Lee

Kingstad-Bakke

Kedl³

et al. 2021

Preprint

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Elicitation of lung tissue-resident memory CD8 T cells (TRMs) is a goal of T-cell based vaccines against respiratory viral pathogens such as influenza A virus (IAV). Chemokine receptor 2 (CCR2)-dependent monocyte trafficking plays an essential role in the establishment of CD8 TRMs in lungs of IAV-infected mice. Here, we used a combination adjuvant-based subunit vaccine strategy that evokes multifaceted (TC1/TC17/TH1/TH17) IAV nucleoprotein-specific lung TRMs, to determine whether CCR2 and monocyte infiltration are essential for vaccine-induced TRM development and protective immunity to IAV in lungs. Following intranasal vaccination, neutrophils, monocytes, conventional dendrtitic cells (DCs) and monocyte-derived DCs internalized and processed vaccine antigen in lungs. We also found that Basic Leucine Zipper ATF-Like Transcription Factor 3 (BATF-3)-dependent DCs were essential for eliciting T cell responses, but CCR2 deficiency enhanced the differentiation of CD127HI/KLRG-1LO, OX40+veCD62L+ve and mucosally imprinted CD69+veCD103+ve effector and memory CD8 T cells in lungs and airways of vaccinated mice. Mechanistically, increased development of lung TRMs, induced by CCR2 deficiency was linked to dampened expression of T-bet, but not altered TCF-1 levels or T cell receptor signaling in CD8 T cells. T1/T17 functional programming, parenchymal localization of CD8/CD4 effector and memory T cells, recall T cell responses and protective immunity to a lethal IAV infection were unaffected in CCR2-deficient mice. Taken together, we identified a negative regulatory role for CCR2 and monocyte trafficking in mucosal imprinting and differentiation of vaccine-induced TRMs. Mechanistic insights from this study may aid the development of T-cell-based vaccines against respiratory viral pathogens including IAV and SARS-CoV-2.

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“…Tissue cytokines have been shown to act synergistically in establishing the resident memory phenotype in tissues such as the gut, skin, brain, and the lungs (40,(44)(45)(46)(47)(48)(49). Hereafter, we will discuss what it is known of how each one of these signals contribute to T RM development and maintenance and discuss the synergism of the signaling pathways they trigger.…”

Section: Tissue Signals Involved In Cd8 T Rm Developmentmentioning

confidence: 99%

“…Comparative in vitro analysis also demonstrates a great overlapping between T RM and TGFβ transcriptional signatures ( 64 ). More precisely, TGFβ signaling regulates the expression of transcription factors involved in T RM development, such as Runx3 ( 65 ) and Blimp1 ( 66 ) and repress transcription factors (Eomes, TCF1, and T-bet) ( 40 , 46 ), which are classically associated with CD8 terminal effector and central memory differentiation ( 5 , 67 – 70 ). Achieving the right balance in the levels of all of these transcription factors appears to be crucial for the development of CD8 T RM .…”

Section: Tissue Signals Involved In Cd8 T Rm Developmentmentioning

confidence: 99%

Interplay of Inflammatory, Antigen and Tissue-Derived Signals in the Development of Resident CD8 Memory T Cells

2021

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CD8 positive, tissue resident memory T cells (TRM) are a specialized subset of CD8 memory T cells that surveil tissues and provide critical first-line protection against tumors and pathogen re-infection. Recently, much effort has been dedicated to understanding the function, phenotype and development of TRM. A myriad of signals is involved in the development and maintenance of resident memory T cells in tissue. Much of the initial research focused on the roles tissue-derived signals play in the development of TRM, including TGFß and IL-33 which are critical for the upregulation of CD69 and CD103. However, more recent data suggest further roles for antigenic and pro-inflammatory cytokines. This review will focus on the interplay of pro-inflammatory, tissue and antigenic signals in the establishment of resident memory T cells.

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T Cell Factor 1 Suppresses CD103+ Lung Tissue-Resident Memory T Cell Development

Cited by 47 publications

References 55 publications

TGF-β: Many Paths to CD103+ CD8 T Cell Residency

TGF-β: Many Paths to CD103+ CD8 T Cell Residency

CCR2 Regulates Vaccine-Induced Mucosal T-Cell Memory to Influenza A Virus

Interplay of Inflammatory, Antigen and Tissue-Derived Signals in the Development of Resident CD8 Memory T Cells

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