Loss of Roquin induces early death and immune deregulation but not autoimmunity

Bertossi, Arianna; Aichinger, Martin; Sansonetti, Paola; Lech, Maciej; Neff, Frauke; Pál, Martin; Wunderlich, Frank; Anders, Hans‐Joachim; Klein, Ludger; Schmidt-Supprian, Marc

doi:10.1084/jem.20110578

Cited by 91 publications

(123 citation statements)

References 19 publications

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“…Loss of Roquin, either specifically on T cells or in the hematopoietic system, caused expansion on CD8 + effector-like T cells but not autoimmunity (28). In contrast, Roquin bearing the san allele, which is a gain-of-function-allele (29, data not shown), causes follicular helper T (Tfh) cell-dependent lupus (30)(31)(32)(33); it is achieved, at least in part, through posttranscriptional regulation of Icos mRNA.…”

Section: Cd8 + T Cells Responding To Viral Infections Initiate Their mentioning

confidence: 96%

Breakdown in Repression of IFN-γ mRNA Leads to Accumulation of Self-Reactive Effector CD8+ T Cells

Chang

Lee

et al. 2012

The Journal of Immunology

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Tight regulation of virus-induced cytotoxic effector CD8+ T cells is essential to prevent immunopathology. Naturally occurring effector CD8+ T cells, with a KLRG1hi CD62Llo phenotype typical of short-lived effector CD8+ T cells (SLECs), can be found in increased numbers in autoimmune-prone mice, most notably in mice homozygous for the san allele of Roquin. These SLEC-like cells were able to trigger autoimmune diabetes in a susceptible background. When Roquin is mutated (Roquinsan), effector CD8+ T cells accumulate in a cell-autonomous manner, most prominently as SLEC-like effectors. Excessive IFN-γ promotes the accumulation of SLEC-like cells, increases their T-bet expression, and enhances their granzyme B production in vivo. We show that overexpression of IFN-γ was caused by failed posttranscriptional repression of Ifng mRNA. This study identifies a novel mechanism that prevents accumulation of self-reactive cytotoxic effectors, highlighting the importance of regulating Ifng mRNA stability to maintain CD8+ T cell homeostasis and prevent CD8-mediated autoimmunity.

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Section: Cd8 + T Cells Responding To Viral Infections Initiate Their mentioning

confidence: 96%

Breakdown in Repression of IFN-γ mRNA Leads to Accumulation of Self-Reactive Effector CD8+ T Cells

Chang

Lee

et al. 2012

The Journal of Immunology

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“…33,34 In addition, a recent study showed that the loss of roquin induced early death and immune dysregulation but not autoimmunity in sanroque mice. 35 Therefore, future studies are required to completely elucidate the mechanisms behind pathogenesis of lupus in sanroque mice. T H -cell differentiation is polarized toward T FH cells to generate B-cell responses against infections.…”

Section: T Fh Cells In Murine Models Of Autoimmune Diseasesmentioning

confidence: 99%

The darker side of follicular helper T cells: from autoimmunity to immunodeficiency

Shekhar

Yang

2012

Cell Mol Immunol

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Follicular helper T (T FH ) cells represent a distinct subset of CD4 1 helper T (T H ) cells specialized in providing help to B cells. They are characterized by their unique transcriptional profile (Bcl6), surface marker expression (CXCR5, PD-1, ICOS and CD40L) and cytokine production pattern (IL-21 and IL-6). T FH cells provide help to B cells both to form germinal centers (GCs) and to differentiate into memory B cells and plasma cells for generation of humoral responses. However, there is emerging evidence that implicates T FH cells in the development of various human pathologies, such as autoimmune diseases, immunodeficiency and lymphoma. This review focuses on the current progress in this area including mouse and human studies. A clearer understanding of the mechanisms of T FH cell-mediated immunity and pathology may be exploited for rational development of therapeutic strategies.

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“…Germ-line Roquin-deficient mice are perinatally lethal, so tissue-specific ablation of Roquin in T cells, B cells, and hematopoietic cells does not cause autoimmunity (24). For gain of function via Roquin overexpression, we established Roquin Tg mice.…”

Section: Discussionmentioning

confidence: 99%

Enforced Expression of Roquin Protein in T Cells Exacerbates the Incidence and Severity of Experimental Arthritis

Kim

et al. 2012

Journal of Biological Chemistry

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Loss of Roquin induces early death and immune deregulation but not autoimmunity

Abstract: Deletion of Roquin in T or B cells, or in the entire hematopoietic system of mice, alters immune homeostasis but does not result in autoimmunity.

Cited by 91 publications

References 19 publications

Breakdown in Repression of IFN-γ mRNA Leads to Accumulation of Self-Reactive Effector CD8+ T Cells

Breakdown in Repression of IFN-γ mRNA Leads to Accumulation of Self-Reactive Effector CD8+ T Cells

The darker side of follicular helper T cells: from autoimmunity to immunodeficiency

Enforced Expression of Roquin Protein in T Cells Exacerbates the Incidence and Severity of Experimental Arthritis

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