Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche

Hirai, Toshiro; Yang, Yi; Zenke, Yukari; Li, Haiyue; Chaudhri, Virendra K.; Diaz, Jacinto S. De La Cruz; Zhou, Paul Yifan; Nguyen, B.A.; Bartholin, Laurent; Workman, Creg J.; Griggs, David W.; Vignali, Dario A.A.; Singh, Harinder; Masopust, David; Kaplan, Daniel H.

doi:10.1016/j.immuni.2020.10.022

Cited by 78 publications

(69 citation statements)

References 50 publications

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“…Several cell types in the epidermis, including Langerhans cells, keratinocytes, dendritic epidermal T cells (DETC), and CD8 T RM cells, can express TGF-β and provide a source to support CD103 + CD8 T RM cell residence [ 66 ]. Nevertheless, continued exposure to TGF-β derived from CD8 T RM cells, but not Langerhans cells, keratinocytes, or DETC, is required for the long-term persistence of epidermal CD103 + CD8 T RM cells [ 64 , 67 , 68 ]. Interestingly, while the presence of antigen in the flank skin is not required for the development of CD103 + CD8 T RM cells, it renders antigen-specific T RM cells more resistant to the impact of limited amounts of TGF-β than recruited bystander T RM cells [ 68 , 69 ].…”

Section: Integrin-mediated Activation Of Tgf-β In the Development And Maintenance Of Cd103 + Cd8 T Rm mentioning

confidence: 99%

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: Integrin-mediated Activation Of Tgf-β In the Development And Maintenance Of Cd103 + Cd8 T Rm mentioning

confidence: 99%

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

Qiu

Chu

Sheridan

2021

Cells

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“…TGF-b induces the expression of CD103 on CD8 + T cells (44). In the skin, CD8 + T RM cells require transactivated autocrine TGF-b for epidermal persistence (45). An important cytokine for the survival of CD8 + T RM cells in the skin is IL-15 (46).…”

Section: The Molecular Mechanisms Underlying the Induction And Maintenance Of The Tissue Residency Of T Rm Cellsmentioning

confidence: 99%

The Role of CD4+ Resident Memory T Cells in Local Immunity in the Mucosal Tissue – Protection Versus Pathology –

et al. 2021

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Memory T cells are crucial for both local and systemic protection against pathogens over a long period of time. Three major subsets of memory T cells; effector memory T (TEM) cells, central memory T (TCM) cells, and tissue-resident memory T (TRM) cells have been identified. The most recently identified subset, TRM cells, is characterized by the expression of the C-type lectin CD69 and/or the integrin CD103. TRM cells persist locally at sites of mucosal tissue, such as the lung, where they provide frontline defense against various pathogens. Importantly, however, TRM cells are also involved in shaping the pathology of inflammatory diseases. A number of pioneering studies revealed important roles of CD8+ TRM cells, particularly those in the local control of viral infection. However, the protective function and pathogenic role of CD4+ TRM cells that reside within the mucosal tissue remain largely unknown. In this review, we discuss the ambivalent feature of CD4+ TRM cells in the protective and pathological immune responses. We also review the transcriptional and epigenetic characteristics of CD4+ TRM cells in the lung that have been elucidated by recent technical approaches. A better understanding of the function of CD4+ TRM cells is crucial for the development of both effective vaccination against pathogens and new therapeutic strategies for intractable inflammatory diseases, such as inflammatory bowel diseases and chronic allergic diseases.

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“…CD8 + T cells expressing mutant TGF-b receptors fail to express CD103 or persist within multiple peripheral tissues (42,43,81,105,109). Recent data suggest that epidermal CD8 + T RM cells require transactivation of autocrine TGF-b for their long-term persistence, and competition for limited TGF-b influences which clones persist within the epidermis (112). CD8 + T cell TGF-b responsiveness is controlled by the transcription factors EOMES and T-bet, and downregulation of Eomes and T-bet is required for CD8 + T cell TGF-b responsiveness and CD8 + T RM formation (94).…”

Section: Tissue-derived Signals: Cytokines Inflammatory Molecules Amentioning

confidence: 99%

Discipline in Stages: Regulating CD8+ Resident Memory T Cells

Mora-Buch

Bromley

2021

Front. Immunol.

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Resident memory CD8+ T (TRM) cells are a lymphocyte lineage distinct from circulating memory CD8+ T cells. TRM lodge within peripheral tissues and secondary lymphoid organs where they provide rapid, local protection from pathogens and control tumor growth. However, dysregulation of CD8+ TRM formation and/or activation may contribute to the pathogenesis of autoimmune diseases. Intrinsic mechanisms, including transcriptional networks and inhibitory checkpoint receptors control TRM differentiation and response. Additionally, extrinsic stimuli such as cytokines, cognate antigen, fatty acids, and damage signals regulate TRM formation, maintenance, and expansion. In this review, we will summarize knowledge of CD8+ TRM generation and highlight mechanisms that regulate the persistence and responses of heterogeneous TRM populations in different tissues and distinct microenvironments.

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Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche

Cited by 78 publications

References 50 publications

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

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

The Role of CD4+ Resident Memory T Cells in Local Immunity in the Mucosal Tissue – Protection Versus Pathology –

Discipline in Stages: Regulating CD8+ Resident Memory T Cells

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