IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis

Huber, Magdalena; Heink, Sylvia; Pagenstecher, Axel; Reinhard, Katharina; Ritter, Josephine; Visekruna, Alexander; Guralnik, Anna; Bollig, Nadine; Jeltsch, Katharina M.; Heinemann, Christina; Wittmann, Eva; Buch, Thorsten; Costa, Olivia Prazeres da; Brüstle, Anne; Brenner, Dirk; Mak, Tak W.; Mittrücker, Hans‐Willi; Tackenberg, Björn; Kamradt, Thomas; Lohoff, Michael

doi:10.1172/jci63681

Cited by 216 publications

(217 citation statements)

References 48 publications

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“…Analysis of TFs in Irf4 −/− CD8 + T cells revealed up-regulation of BCL-6, Eomes, and Id3. We and others have recently described high Eomes expression in Irf4 −/− CD8 + T cells (25,26). High expression of BCL-6, Eomes and Id3 and low expression of Blimp-1, Id2, and T-bet are associated with the development of memory CD8 + T cells (1).…”

Section: Discussionmentioning

confidence: 83%

“…Whole-cell lysates were prepared from purified CD8 + T cells without stimulation or after in vitro stimulation. Immunoblotting was performed, as described previously (26). Briefly, proteins were fractionated by SDS/ PAGE, transferred to nitrocellulose membrane, immunoblotted with pSTAT3 Tyr705 (9131; Cell Signaling Technology), IRF4 (M-17; sc6059; Santa Cruz) or Blimp-1 (Novus) antibodies, and then reprobed with antibodies to total STAT3 (124H6; 9139; Cell Signaling Technology) or β-Actin (Sigma-Aldrich).…”

Section: Discussionmentioning

confidence: 99%

“…IRF4-deficient (Irf4 −/− ) mice are impaired in their response to lymphocytic choriomeningitis virus infection (24) and IRF4 appears to control expression of Eomes in these cells (25,26). Here, we investigate the role of IRF4 in CD8 + T cells during an immune response against the intracellular bacterium Listeria monocytogenes and demonstrate an intrinsic role for IRF4 in the differentiation of peripheral cytotoxic T lymphocytes.…”

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confidence: 99%

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The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8 ⁺ T cells

Raczkowski

Ritter

Heesch

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Robust cytotoxic CD8 + T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8 + T-cell response to the intracellular bacterium Listeria monocytogenes. IRF4-deficient (Irf4 −/− ) mice could not clear L. monocytogenes infection and generated decreased numbers of L. monocytogenesspecific CD8 + T cells with impaired effector phenotype and function. Transfer of wild-type CD8 + T cells into Irf4 −/− mice improved bacterial clearance, suggesting an intrinsic defect of CD8 + T cells in Irf4 −/− mice. Following transfer into wild-type recipients, Irf4 −/− CD8 + T cells became activated and showed initial proliferation upon L. monocytogenes infection. However, these cells could not sustain proliferation, produced reduced amounts of IFN-γ and TNF-α, and failed to acquire cytotoxic function. Forced IRF4 expression in Irf4 −/− CD8 + T cells rescued the defect. During acute infection, Irf4 −/− CD8 + T cells demonstrated diminished expression of B lymphocyte-induced maturation protein-1 (Blimp-1), inhibitor of DNA binding (Id)2, and T-box expressed in T cells (T-bet), transcription factors programming effector-cell generation. IRF4 was essential for expression of Blimp-1, suggesting that altered regulation of Blimp-1 contributes to the defects of Irf4 −/− CD8 + T cells. Despite increased levels of B-cell lymphoma 6 (BCL-6), Eomesodermin, and Id3, Irf4 −/− CD8 + T cells showed impaired memory-cell formation, indicating additional functions for IRF4 in this process. As IRF4 governs B-cell and CD4 + T-cell differentiation, the identification of its decisive role in peripheral CD8 + T-cell differentiation, suggests a common regulatory function for IRF4 in adaptive lymphocytes fate decision.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8 ⁺ T cells

Raczkowski

Ritter

Heesch

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…The transcription factor IRF4 is also important for Tc17 differentiation. IRF4 coordinates Tc17 differentiation as positive regulator of RORct and RORa expression as well as a suppressor of transcription factors contributing to Tc1 and Treg development, Eomes and Foxp3, respectively (Huber et al 2013). In comparison to Tc1 cells, Tc17 cells express the transcription factors T-bet and Eomes at diminished levels and probably therefore their properties differ from those of Tc1 cells.…”

Section: Tc17 Cellsmentioning

confidence: 99%

“…In a mouse model for autoimmunity of the central nervous system (CNS), Tc17 cells alone are also not pathogenic, but promote Th17-mediated experimental autoimmune encephalomyelitis (EAE) (Huber et al 2013). The ''reverse help'' of Tc17 cells towards enhanced pathogenicity of Th17 cells requires IL-17 expression by Tc17 cells.…”

Section: Cd8 ? T Cells Lacking Both T-bet and Eomes Fail To Differementioning

confidence: 99%

Heterogeneity in the Differentiation and Function of CD8+ T Cells

Mittrücker

Visekruna

Huber

2014

Arch. Immunol. Ther. Exp.

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It is well established that CD8? T cells constitute an important branch of adaptive immunity contributing to clearance of intracellular pathogens and providing long-term protection. These functions are mostly fulfilled by the best characterized subpopulation of CD8? T cells, the cytotoxic T lymphocytes (also called Tc1 cells), owing to their ability to kill infected cells and to secrete cytokines such as interferon-c and tumor necrosis factor-a. However, there is growing evidence for alternative CD8?

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Roles of CD4 and CD8 T Lymphocytes in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Arbour¹,

Prat²

2015

Neuroinflammation

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IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis

Cited by 216 publications

References 48 publications

The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8 ⁺ T cells

The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8 ⁺ T cells

Heterogeneity in the Differentiation and Function of CD8+ T Cells

Roles of CD4 and CD8 T Lymphocytes in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

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IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis

Cited by 216 publications

References 48 publications

The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8 + T cells

The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8 + T cells

Heterogeneity in the Differentiation and Function of CD8+ T Cells

Roles of CD4 and CD8 T Lymphocytes in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Contact Info

Product

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The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8 ⁺ T cells

The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8 ⁺ T cells