Cutting Edge: Induction of Inflammatory Disease by Adoptive Transfer of an Atypical NK Cell Subset

Voynova, Elisaveta; Qi, Chen‐Feng; Scott, Bethany; Bolland, Silvia

doi:10.4049/jimmunol.1500540

Cited by 11 publications

(21 citation statements)

References 23 publications

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“…In addition, they suggest that NK cells might also contribute to this axis of protection as β2m also regulates the development of this lineage. Contrary to this idea, we recently found that genetic ablation of the IL-15 gene, which is required for normal NK cell development and function, ameliorates disease in TLR7[Tg] mice and suggests an exacerbating effect of cells of the NK cell lineage5657. In the present study, we demonstrate that unlike TLR7[Tg] NK cells, the CD8 + T cells in these mice are not deleterious and may contribute to reducing systemic pathology.…”

Section: Discussioncontrasting

confidence: 76%

Non-pathogenic tissue-resident CD8+ T cells uniquely accumulate in the brains of lupus-prone mice

Morawski

Bolland

2017

Sci Rep

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Severe lupus often includes psychiatric and neurological sequelae, although the cellular contributors to CNS disease remain poorly defined. Using intravascular staining to discriminate tissue-localized from blood-borne cells, we find substantial accumulation of CD8+ T cells relative to other lymphocytes in brain tissue, which correlates with lupus disease and limited neuropathology. This is in contrast to all other affected organs, where infiltrating CD4+ cells are predominant. Brain-infiltrating CD8+ T cells represent an activated subset of those found in the periphery, having a resident-memory phenotype (CD69+CD122−PD1+CD44+CD62L−) and expressing adhesion molecules (VLA-4+LFA-1+) complementary to activated brain endothelium. Remarkably, infiltrating CD8+ T cells do not cause tissue damage in lupus-prone mice, as genetic ablation of these cells via β2 m deficiency does not reverse neuropathology, but exacerbates disease both in the brain and globally despite decreased serum IgG levels. Thus, lupus-associated inflammation disrupts the blood-brain barrier in a discriminating way biased in favor of non-pathogenic CD8+ T cells relative to other infiltrating leukocytes, perhaps preventing further tissue damage in such a sensitive organ.

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Section: Discussioncontrasting

confidence: 76%

Non-pathogenic tissue-resident CD8+ T cells uniquely accumulate in the brains of lupus-prone mice

Morawski

Bolland

2017

Sci Rep

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“…CD226 + NK cells found in the kidney of MRL/lpr mice are associated with renal disease [51]. Adoptive transfer of NK cells from TLR7 transgenic lupus-prone mice is sufficient to induce lupus-like disease in wild type recipients, while genetic ablation of these cells by removal of a critical growth factor, IL-15, greatly reduced pathology in these mice [52]. The atypical NK cells that develop in this model of murine lupus turn on a highly inflammatory and proliferative program and fail to differentiate into a fully mature state [53].…”

Section: Chronic Activation Of Lymphocytes In Sle: B Cells Do Not mentioning

confidence: 99%

Expanding the B Cell-Centric View of Systemic Lupus Erythematosus

Morawski

Bolland

2017

Trends in Immunology

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Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a breakdown of self-tolerance in B cells and production of antibodies against nuclear self-antigens. Increasing evidence supports the notion that additional cellular contributors beyond B cells are important for lupus pathogenesis. In this Review, we consider recent advances regarding both pathogenic and regulatory roles of lymphocytes in SLE, beyond the production of IgG autoantibodies. We also discuss various inflammatory effector cell types involved in cytokine production, removal of self-antigens, and responses to autoreactive IgE antibodies. We aim to integrate these ideas to expand the current understanding of the cellular components that contribute to disease progression and ultimately help in the design of novel targeted therapeutics.

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“…New subsets of NK cells, referred to as NK : DC or atypical NK cells [24,25,29], have been described. These NK cell subsets are characterized by the co-expression of NK cell markers, including NK1.1 and some DCs markers, including CD11c, MHC-II and co-stimulatory molecules.…”

Section: Identification Of a New Subset Of Cd11c 1 Hla-dr 1 Nk Cells mentioning

confidence: 99%

“…This NK cell population could present antigen efficiently, and could induce autoimmune disease [24,25]. This NK cell population could present antigen efficiently, and could induce autoimmune disease [24,25].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of the regulatory function of natural killer cells from patients with systemic lupus erythematosus

Cruz-González

Gómez‐Martín

Layseca-Espinosa

et al. 2017

Clinical and Experimental Immunology

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Natural killer (NK) cells participate in the regulation of the immune response. However, the immunomodulatory function of NK cells in systemic lupus erythematosus (SLE) is not well understood. The aim of this study was to evaluate the regulatory function of NK cells in SLE patients and to identify the NK cells involved in the pathogenesis of this complex disease. We analysed the expression of NK receptors and co-stimulatory molecules in peripheral NK cells (CD3 CD56 ) from SLE patients, as well as the numbers of human leucocyte antigen D-related (HLA-DR)/CD11c NK cells. In addition, NK cell regulatory function was assessed by the detection of NK cell-mediated dendritic cell (DC) lysis. We found that SLE patients showed increased numbers of immunoglobulin-like transcript 2 (ILT2) , CD86 and CD134 NK cells. Furthermore, NK cells from SLE patients induced higher levels of DC lysis. We were able to identify a new subset of NK cells co-expressing CD11c and HLA-DR. These atypical NK cells were increased in SLE patients when compared with controls. We have identified an expanded new subset of NK cells in SLE patients. This is the first study, to our knowledge, which demonstrates that NK cells in SLE patients have an altered phenotype with a high expression of receptors characteristic of dendritic cells. Our results suggest that the impairment in the regulatory function of NK cells, together with the increased number of DC-like NK cells, could play an important role in the development of SLE and highlight the importance of NK cells as a future therapeutic target.

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Cutting Edge: Induction of Inflammatory Disease by Adoptive Transfer of an Atypical NK Cell Subset

Cited by 11 publications

References 23 publications

Non-pathogenic tissue-resident CD8+ T cells uniquely accumulate in the brains of lupus-prone mice

Non-pathogenic tissue-resident CD8+ T cells uniquely accumulate in the brains of lupus-prone mice

Expanding the B Cell-Centric View of Systemic Lupus Erythematosus

Analysis of the regulatory function of natural killer cells from patients with systemic lupus erythematosus

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