DX5<sup>+</sup>NKT cells induce the death of colitis‐associated cells: involvement of programmed death ligand‐1

Hornung, Matthias; Farkas, S.; Sattler, Christine; Geissler, Edward K.

doi:10.1002/eji.200535332

Cited by 29 publications

(32 citation statements)

References 53 publications

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“…Mice subjected to DS for 6 hours, 1 day, or 5 days received intraperitoneal injections (IP) of anti-NK1.1 antibody (PK136) (20) or i.p. injections of mouse-IgG isotype control (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Desiccating Stress–Induced Chemokine Expression in the Epithelium Is Dependent on Upregulation of NKG2D/RAE-1 and Release of IFN-γ in Experimental Dry Eye

Coursey

Bohat

Barbosa

et al. 2014

The Journal of Immunology

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The Th1-associated chemokines CXCL-9, CXCL-10, CXCL-11 coordinate migration of CXCR3+Th1 cells. The objective of this study was to evaluate the role of the innate immune system in stimulating chemokine expression in an experimental model of dry eye and bridge the gap between innate and adaptive immunity. Desiccating stress (DS) induced very early (six hours) expression and production of Th1-associated chemokine in cornea and conjunctiva of C57BL/6 and recombination activating gene 1 (RAG1) knock out (KO) strains, demonstrating that chemokine expression does not require innate T cells. We then demonstrated that activating the innate immune system prior to adoptive transfer of T cells to RAG1KO increased disease severity. Interestingly, lack of induction of chemokines CXCL-9, CXCL-10, CXCL-11 in IFN-γKO mice, provided evidence that their expression requires IFN-γ for induction. Treatment of RAG1KO mice with anti-NK1.1 prevented the increase of CXCL9, CXCL10, and CXCL11 in response to DS, compared to isotype controls. Additionally, DS increased the expression of NKG2D in the conjunctiva. The expression of the NKG2D ligand, RAE-1, also increased at the ocular surface at both the protein and gene level. Neutralization of NKG2D at the ocular surface decreased the expression of CXCL-9, CXCL-10, CXCL-11 and IFN-γ. In summary, upregulation of CXCL9, CXCL-10, and CXCL-11 expression in experimental dry eye is T cell independent, requiring IFN-γ-producing NKG2D+ NK cells that are activated in response to DS induced stress signals. This work provides insight about the events that trigger the initial immune response in dry eye pathology.

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Section: Methodsmentioning

confidence: 99%

Desiccating Stress–Induced Chemokine Expression in the Epithelium Is Dependent on Upregulation of NKG2D/RAE-1 and Release of IFN-γ in Experimental Dry Eye

Coursey

Bohat

Barbosa

et al. 2014

The Journal of Immunology

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“…In a colitis model induced by the adoptive transfer of naïve CD4 + T cells into SCID mice, CD1d was found to be upregulated on colonic epithelial cells. 22 In addition, co-transfer of DX5 + NKT cells prevented the development of disease in recipient mice, indicating that the activation of NKT cells may be protective in this IBD model. In contrast, a deleterious role for type I NKT cells has been described in oxazolone-induced colitis.…”

Section: Introductonmentioning

confidence: 93%

Dysregulation of CD1d-Restricted Type II Natural Killer T Cells Leads to Spontaneous Development of Colitis in Mice

et al. 2012

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Background & Aims CD1d-restricted natural killer (NK) T cells are a subset of immunoregulatory T cells that comprise type I (express the semi-invariant T-cell receptor [TCR] and can be detected using the α-GalCer/CD1d tetramer) and type II (express diverse TCRs and cannot be directly identified). Studies in mouse models of inflammatory bowel disease revealed a complex role for type I NKT cells in the development of colitis. Type II NKT cells have been associated with intestinal inflammation in patients with ulcerative colitis. Method To investigate whether dysregulation of type II NKT cells, caused by increased expression of CD1d, can contribute to colitis, we generated transgenic mice that express high levels of CD1d and a TCR from an autoreactive, type II NKT cell (CD1dTg/24αβTg mice). Results CD1dTg/24αβTg mice had reduced numbers of 24αβ T cells, compared with 24αβTg mice, indicating that negative selection increases among type II NKT cells engaged by abundant self-antigen. The residual 24αβ T cells in CD1dTg/24αβTg mice had an altered surface phenotype and acquired a cytokine profile distinct from that of equivalent cells in 24αβTg mice. Interestingly, CD1dTg/24αβTg mice spontaneously developed colitis; adoptive transfer experiments confirmed that type II NKT cells that develop in the context of increased CD1d expression are pathogenic. Conclusions Aberrant type II NKT cell responses directly contribute to intestinal inflammation in mice, indicating the importance of CD1d expression levels in the development and regulation of type II NKT cells.

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“…In the transfer model of colitis, cotransfer of T cells expressing the NK receptor DX5 with the pathogenic CD4 T cells ameliorated disease, and this effect could be blocked by injection of an anti-CD1d antibody (21). However, because only a minority of DX5 ϩ NKT cells are CD1d dependent (45), it is not certain which NKT cell population was responsible for the protection, and, given the induction of IL-10 by anti-CD1d, it is possible that the antibody triggered CD1d functions independent of their interactions with subsets of NKT cells.…”

Section: Nkt Cells In Inflammatory Bowel Diseasementioning

confidence: 97%

Role of NKT cells in the digestive system. IV. The role of canonical natural killer T cells in mucosal immunity and inflammation

Wingender¹,

Kronenberg²

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Lymphocytes that combine features of T cells and natural killer (NK) cells are named natural killer T (NKT) cells. The majority of NKT cells in mice bear highly conserved invariant Valpha chains, and to date two populations of such canonical NKT cells are known in mice: those that express Valpha14 and those that express Valpha7.2. Both populations are selected by nonpolymorphic major histocompatibility complex class I-like antigen-presenting molecules expressed by hematopoietic cells in the thymus: CD1d for Valpha14-expressing NKT cells and MR1 for those cells expressing Valpha7.2. The more intensely studied Valpha14 NKT cells have been implicated in diverse immune reactions, including immune regulation and inflammation in the intestine; the Valpha7.2 expressing cells are most frequently found in the lamina propria. In humans, populations of canonical NKT cells are found to be highly similar in terms of the expression of homologous, invariant T cell antigen-receptor alpha-chains, specificity, and function, although their frequency differs from those in the mouse. In this review, we will focus on the role of both of these canonical NKT cell populations in the mucosal tissues of the intestine.

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DX5⁺NKT cells induce the death of colitis‐associated cells: involvement of programmed death ligand‐1

Cited by 29 publications

References 53 publications

Desiccating Stress–Induced Chemokine Expression in the Epithelium Is Dependent on Upregulation of NKG2D/RAE-1 and Release of IFN-γ in Experimental Dry Eye

Desiccating Stress–Induced Chemokine Expression in the Epithelium Is Dependent on Upregulation of NKG2D/RAE-1 and Release of IFN-γ in Experimental Dry Eye

Dysregulation of CD1d-Restricted Type II Natural Killer T Cells Leads to Spontaneous Development of Colitis in Mice

Role of NKT cells in the digestive system. IV. The role of canonical natural killer T cells in mucosal immunity and inflammation

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DX5+NKT cells induce the death of colitis‐associated cells: involvement of programmed death ligand‐1

Cited by 29 publications

References 53 publications

Desiccating Stress–Induced Chemokine Expression in the Epithelium Is Dependent on Upregulation of NKG2D/RAE-1 and Release of IFN-γ in Experimental Dry Eye

Desiccating Stress–Induced Chemokine Expression in the Epithelium Is Dependent on Upregulation of NKG2D/RAE-1 and Release of IFN-γ in Experimental Dry Eye

Dysregulation of CD1d-Restricted Type II Natural Killer T Cells Leads to Spontaneous Development of Colitis in Mice

Role of NKT cells in the digestive system. IV. The role of canonical natural killer T cells in mucosal immunity and inflammation

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DX5⁺NKT cells induce the death of colitis‐associated cells: involvement of programmed death ligand‐1