BATF3 programs CD8+ T cell memory

Ataide, Marco A.; Komander, Karl; Knöpper, Konrad; Peters, Annika E.; Wu, Hao; Eickhoff, Sarah; Gogishvili, Tea; Weber, Justus; Grafen, Anika; Kallies, Axel; Garbi, Natalio; Einsele, Hermann; Hudecek, Michael; Gasteiger, Georg; Hölzel, Michael; Vaeth, Martin; Kastenmüller, Wolfgang

doi:10.1038/s41590-020-0786-2

Cited by 83 publications

(55 citation statements)

References 52 publications

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“…For example, it inhibits the differentiation of regulatory T cells in the periphery (20). Very recently, a role for Batf3 in memory CD8 + T cell differentiation has been revealed (21,22). Importantly, Batf3 selectively determines acquisition of CD8a + DC phenotype and function in lymphoid organs, and CD103 + in non-lymphoid organs (15,(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Resistance to Experimental Visceral Leishmaniasis in Mice Infected With Leishmania infantum Requires Batf3

et al. 2020

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Unveiling the protective immune response to visceral leishmaniasis is critical for a rational design of vaccines aimed at reducing the impact caused by this fatal, if left untreated, vector-borne disease. In this study we sought to determine the role of the basic leucine zipper transcription factor ATF-like 3 (Batf3) in the evolution of infection with Leishmania infantum, the causative agent of human visceral leishmaniasis in the Mediterranean Basin and Latin America. For that, Batf3-deficient mice in C57BL/6 background were infected with an L. infantum strain expressing the luciferase gene. Bioluminescent imaging, as well as in vitro parasite titration, demonstrated that Batf3-deficient mice were unable to control hepatic parasitosis as opposed to wild-type C57BL/6 mice. The impaired microbicide capacities of L. infantum-infected macrophages from Batf3-deficient mice mainly correlated with a reduction of parasite-specific IFN-γ production. Our results reinforce the implication of Batf3 in the generation of type 1 immunity against infectious diseases.

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Section: Discussionmentioning

confidence: 99%

Resistance to Experimental Visceral Leishmaniasis in Mice Infected With Leishmania infantum Requires Batf3

et al. 2020

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“…While this may be true in some settings [e.g., antitumor CTL responses absolutely require cross priming (251)], it could also reflect another nonredundant activity of cDC1s, such as the aforementioned IL-12 production, which protects from infection by T. gondii (252). In some cases, it could even reflect a cDC1-independent effect of Batf3 loss on the T cells themselves (253,254). It should be remembered that, in the context of viral infection, even if cross presentation dominates in many instances (220), infected cDC1s can present viral antigens directly (255).…”

Section: Revisiting Dogmas About Conventional Dendritic Cell Subset Function In Antigen Presentationmentioning

confidence: 99%

Dendritic Cells Revisited

Cabeza-Cabrerizo

Cardoso

Minutti

et al. 2021

Annu. Rev. Immunol.

367

362

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Dendritic cells (DCs) possess the ability to integrate information about their environment and communicate it to other leukocytes, shaping adaptive and innate immunity. Over the years, a variety of cell types have been called DCs on the basis of phenotypic and functional attributes. Here, we refocus attention on conventional DCs (cDCs), a discrete cell lineage by ontogenetic and gene expression criteria that best corresponds to the cells originally described in the 1970s. We summarize current knowledge of mouse and human cDC subsets and describe their hematopoietic development and their phenotypic and functional attributes. We hope that our effort to review the basic features of cDC biology and distinguish cDCs from related cell types brings to the fore the remarkable properties of this cell type while shedding some light on the seemingly inordinate complexity of the DC field. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…Hence, mouse models targeting cDC1 with a higher specificity are mandatory to investigate whether and how they contribute to antitumor immunity. 27 This is the case of mice knocked-in for the CRE recombinase in the Xcr1 locus. 29 Several key features of cDC1 are proposed to contribute to their critical role in antitumor immunity, beyond their efficiency at crosspresenting cell-associated Ag.…”

Section: Introductionmentioning

confidence: 99%

“…Irf8 deficiency in CD11c‐expressing cells also affected the differentiation and functions of plasmacytoid dendritic cells 23 and inflammatory cDC2 24 . Batf3 knockout does not only abrogate cDC1 differentiation 25 but was also recently shown to enhance CD4 + regulatory T‐cell (Treg) induction 26 and to hamper CTL survival and memory 27,28 in a cell‐intrinsic manner. Hence, mouse models targeting cDC1 with a higher specificity are mandatory to investigate whether and how they contribute to antitumor immunity 27 .…”

Section: Introductionmentioning

confidence: 99%

Type 1 conventional dendritic cells and interferons are required for spontaneous CD4⁺ and CD8⁺ T‐cell protective responses to breast cancer

et al. 2021

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Objectives. To better understand how immune responses may be harnessed against breast cancer, we investigated which immune cell types and signalling pathways are required for spontaneous control of a mouse model of mammary adenocarcinoma. Methods. The NOP23 mammary adenocarcinoma cell line expressing epitopes derived from the ovalbumin model antigen is spontaneously controlled when orthotopically engrafted in syngeneic C57BL/6 mice. We combined this breast cancer model with antibodymediated depletion of lymphocytes and with mutant mice affected in interferon (IFN) or type 1 conventional dendritic cell (cDC1) responses. We monitored tumor growth and immune infiltration including the activation of cognate ovalbumin-specific T cells. Results. Breast cancer immunosurveillance required cDC1, NK/NK T cells, conventional CD4 + T cells and CD8 + cytotoxic T lymphocytes (CTLs). cDC1 were required constitutively, but especially during Tcell priming. In tumors, cDC1 were interacting simultaneously with CD4 + T cells and tumor-specific CTLs. cDC1 expression of the XCR1 chemokine receptor and of the T-cell-attracting or T-cell-activating cytokines CXCL9, IL-12 and IL-15 was dispensable for tumor rejection, whereas IFN responses were necessary, including cDC1intrinsic signalling by STAT1 and IFN-γ but not type I IFN (IFN-I). cDC1 and IFNs promoted CD4 + and CD8 + T-cell infiltration, terminal differentiation and effector functions. In breast cancer patients, high intratumor expression of genes specific to cDC1, CTLs, CD4 + T cells or IFN responses is associated with a better prognosis. Conclusion. Interferons and cDC1 are critical for breast cancer immunosurveillance. IFN-γ plays a prominent role over IFN-I in licensing cDC1 for efficient T-cell activation.

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BATF3 programs CD8+ T cell memory

Cited by 83 publications

References 52 publications

Resistance to Experimental Visceral Leishmaniasis in Mice Infected With Leishmania infantum Requires Batf3

Resistance to Experimental Visceral Leishmaniasis in Mice Infected With Leishmania infantum Requires Batf3

Dendritic Cells Revisited

Type 1 conventional dendritic cells and interferons are required for spontaneous CD4⁺ and CD8⁺ T‐cell protective responses to breast cancer

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BATF3 programs CD8+ T cell memory

Cited by 83 publications

References 52 publications

Resistance to Experimental Visceral Leishmaniasis in Mice Infected With Leishmania infantum Requires Batf3

Resistance to Experimental Visceral Leishmaniasis in Mice Infected With Leishmania infantum Requires Batf3

Dendritic Cells Revisited

Type 1 conventional dendritic cells and interferons are required for spontaneous CD4+ and CD8+ T‐cell protective responses to breast cancer

Contact Info

Product

Resources

About

Type 1 conventional dendritic cells and interferons are required for spontaneous CD4⁺ and CD8⁺ T‐cell protective responses to breast cancer