IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset

Sağ, Duygu; Krause, Petra; Hedrick, Catherine C.; Kronenberg, Mitchell; Wingender, Gerhard

doi:10.1172/jci72308

Cited by 226 publications

(297 citation statements)

References 74 publications

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“…The present study has provided novel evidence to show that a novel fraction of NKT cells has immune suppressor functions on CD8 data show that the glioma-derived NKT cells not only express IL-10, but more than 90% cells also express IL-6. The fact suggests that the glioma-derived NKT cells are different from those reported by Sag et al (13). NKT cells have miscellaneous functions; one of which is the antitumor function by releasing a number of antitumor cytokines, including those from Th1 cells, Th2 cells, and cytotoxic CD8 ϩ T cells.…”

Section: Discussionmentioning

confidence: 68%

Activation of Glioma Cells Generates Immune Tolerant NKT Cells

Tang

Wei

et al. 2014

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 68%

Activation of Glioma Cells Generates Immune Tolerant NKT Cells

Tang

Wei

et al. 2014

Journal of Biological Chemistry

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“…Recent data from Wingender and coworkers (49) have suggested that iNKT cells previously activated by αGalCer become IL-10-producing iNKT10 cells. Thus, IL-10 from iNKT cells may dominate the response to expand MZB cells and maintain T FR cells under conditions where there are no inflammatory cytokines from T FH cells to override this regulatory environment and expand B effector cells and inhibit T FR cells.…”

Section: Discussionmentioning

confidence: 99%

Cognate interaction with iNKT cells expands IL-10–producing B regulatory cells

Vomhof-DeKrey

Yates

Hägglöf

et al. 2015

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

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Successful induction of B-cell activation and memory depends on help from CD4 + T cells. Invariant natural killer T (iNKT) cells (glycolipid-specific, CD1d-restricted innate lymphocytes) provide both cognate (direct) and noncognate (indirect) helper signals to enhance B-cell responses. Both forms of iNKT-cell help induce primary humoral immune responses, but only noncognate iNKT-cell help drives humoral memory and plasma cells. Here, we show that iNKT cognate help for B cells is fundamentally different from the help provided by conventional CD4 + T cells. Cognate iNKT-cell help drives an early, unsustained germinal center B-cell expansion, less reduction of T follicular regulatory cells, an expansion of marginal zone B cells, and early increases in regulatory IL-10-producing B-cell numbers compared with noncognate activation. These results are consistent with a mechanism whereby iNKT cells preferentially provide an innate form of help that does not generate humoral memory and has important implications for the application of glycolipid molecules as vaccine adjuvants.

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“…Thus, we have explored an alternative immune regulatory population, iNKT cells, that are not exquisitely IL-2 sensitive and are highly effective in limited cell numbers in preventing acute GVHD (aGVHD). [4][5][6] iNKT cells have immune regulation function, 7 conferred by the rapid production of immune regulatory cytokines such as IL-4 and IL-10, 8,9 and promote Treg expansion, perhaps through a myeloid cell intermediate. 5,10 iNKT deficiency has been linked to autoimmune diseases (eg, type 1 diabetes, rheumatoid arthritis, and lupus).…”

Section: Introductionmentioning

confidence: 99%

Invariant natural killer T cells ameliorate murine chronic GVHD by expanding donor regulatory T cells

Paz²,

Thangavelu³

et al. 2017

Blood

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• Low doses of donor iNKT infusion prevent and reverse murine cGVHD.• iNKT efficacy in treating established cGVHD is dependent on donor Treg expansion.Chronic graft-versus-host-disease (cGVHD) can cause multiorgan system disease, typically with autoimmune-like features, resulting in high mortality and morbidity caused by treatment limitations. Invariant natural killer T cells (iNKTs), a small population characterized by expression of a semi-invariant T-cell receptor, rapidly produce copious amounts of diverse cytokines on activation that exert potent immune regulatory function.Here, we show that iNKTs are significantly reduced in a cGVHD murine model that recapitulates several aspects of autoimmunity and organ fibrosis observed in patients with cGVHD. Low iNKT infused doses effectively prevented and, importantly, reversed established cGVHD, as did third-party iNKTs. iNKTs suppressed the autoimmune response by reducing the germinal center (GC) reaction, which was associated with an increase in total Tregs and follicular Tregs (Tfr) that control the GC reaction, along with pathogenic antibody production. Treg depletion during iNKT infusions completely abolished iNKT efficacy in treating cGVHD. iNKT cell interleukin 4 production and GC migration were critical to cGVHD reversal. In vivo stimulation of iNKT cells by a-galactosyl-ceramide was effective in both preventing and treating cGVHD. Together, this study demonstrates iNKT deficiency in cGVHD mice and highlights the key role of iNKTs in regulating cGVHD pathogenesis and as a potentially novel prophylactic and therapeutic option for patients with cGVHD. (Blood. 2017;129(23):3121-3125)

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IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset

Cited by 226 publications

References 74 publications

Activation of Glioma Cells Generates Immune Tolerant NKT Cells

Activation of Glioma Cells Generates Immune Tolerant NKT Cells

Cognate interaction with iNKT cells expands IL-10–producing B regulatory cells

Invariant natural killer T cells ameliorate murine chronic GVHD by expanding donor regulatory T cells

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