Host immunomodulatory lipids created by symbionts from dietary amino acids

Oh, Sungwhan F.; Praveena, T.; Song, Huacan; Yoo, Ji-Sun; Jung, Da-Jung; Ertürk-Hasdemir, Deniz; Hwang, Yoon Soo; Lee, ChangWon C.; Nours, Jérôme Le; Kim, Hyunsoo; Lee, Jesang; Blumberg, Richard S.; Rossjohn, Jamie; Park, Seung Bum; Kasper, Dennis L.

doi:10.1038/s41586-021-04083-0

Cited by 76 publications

(75 citation statements)

References 52 publications

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“…Therefore, CAIT cells may be potentially reactive towards microbiome metabolites or small lipids, which were recently shown to modulate NKT cell responses in the gut. 37 The study herewith described also has limitations that we want to highlight here. In our study, we were able to control for only some confounding factors such as age, sex, disease activity, smoking behaviour and anti-TNF treatment, while other factors such as medication and disease history may impact on the observed cell population.…”

Section: Discussionmentioning

confidence: 98%

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A novel unconventional T cell population enriched in Crohn’s disease

Rosati

Martini

Pogorelyy

et al. 2022

Gut

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ObjectiveOne of the current hypotheses to explain the proinflammatory immune response in IBD is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of patients with IBD and controls.DesignWe performed bulk TCR repertoire profiling of both the TCR alpha and beta chains using high-throughput sequencing in peripheral blood samples of a total of 244 patients with IBD and healthy controls as well as from matched blood and intestinal tissue of 59 patients with IBD and disease controls. We further characterised specific T cell clonotypes via single-cell RNAseq.ResultsWe identified a group of clonotypes, characterised by semi-invariant TCR alpha chains, to be significantly enriched in the blood of patients with Crohn’s disease (CD) and particularly expanded in the CD8+ T cell population. Single-cell RNAseq data showed an innate-like phenotype of these cells, with a comparable gene expression to unconventional T cells such as mucosal associated invariant T and natural killer T (NKT) cells, but with distinct TCRs.ConclusionsWe identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population. The potential implications of this population for CD or a subset thereof remain to be elucidated, and the immunophenotype and antigen reactivity of CAIT cells need further investigations in future studies.

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Section: Discussionmentioning

confidence: 98%

“…The cells identified by Almeida et al are reactive to small lipids produced by the microbiome as well as to PentamethylBenzofuranSulfonates (PBFs). Therefore, CAIT cells may be potentially reactive towards microbiome metabolites or small lipids, which were recently shown to modulate NKT cell responses in the gut 37…”

Section: Discussionmentioning

confidence: 99%

A novel unconventional T cell population enriched in Crohn’s disease

Rosati

Martini

Pogorelyy

et al. 2022

Gut

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“…Completing these observations, GM-derived lipids displayed iNKT cell agonistic activity when presented by plate-bound CD1d in vitro, as evidenced by a side-by-side comparison with the prototypical iNKT cell agonist galactosylceramide (Figure 1f). GM-derived lipids may thus have both iNKT cell stimulatory and regulatory properties, similarly to recently described endobiotic glycosphingolipids (Oh et al, 2021).…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 55%

Goat Milk–Derived Lipids Restrain NK T Cell–Dependent Eosinophilic Inflammation in a Murine Model of Atopic Dermatitis

Woods

Cait

Gell

et al. 2022

Journal of Investigative Dermatology

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“…It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted February 13, 2022. ; https://doi.org/10.1101/2022.02.13.480233 doi: bioRxiv preprint ceramides (BfaGC) and subsequently activating NKT cells (e.g. upregulating IL-2 expression) (31). More recently, B. cellulosilyticus has been reported to be enriched in humanized microbiome mouse model of glioma and is a potential contributor to the enhanced efficacy of anti-PD-1 therapy (25).…”

Section: Discussionmentioning

confidence: 99%

“…Additional immunomodulatory function of B. fragilis includes producing unique alpha-galactose ceramides (BfaGC) and subsequently activating NKT cells (e.g. upregulating IL-2 expression) (31). More recently, B. cellulosilyticus has been reported to be enriched in humanized microbiome mouse model of glioma and is a potential contributor to the enhanced efficacy of anti-PD-1 therapy (25).…”

Section: Discussionmentioning

confidence: 99%

Metagenomic and Metabolomic Analyses Reveal Synergistic Effects of Fecal Microbiota Transplantation and Anti-PD-1 Therapy on Treating Colorectal Cancer

Huang

Zheng

Kang

et al. 2022

Preprint

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Anti-PD-1 immunotherapy has saved numerous lives of cancer patients; however, it only exerts efficacy in 10-15% of patients with colorectal cancer. Fecal microbiota transplantation (FMT) is a potential approach to improving the efficacy of anti-PD-1 therapy, whereas the detailed mechanisms and the applicability of this combination therapy remain unclear. In this study, we evaluated the synergistic effect of FMT with anti-PD-1 in curing colorectal tumor-bearing mice using a multi-omics approach. Mice treated with the combination therapy showed superior survival rate and tumor control, compared to the mice received anti-PD-1 therapy or FMT alone. Metagenomic analysis showed that composition of gut microbiota in tumor-bearing mice treated with anti-PD-1 therapy was remarkably altered through receiving FMT. Particularly, Bacteroides genus, including FMT-increased B. thetaiotaomicron, B. fragilis, and FMT-decreased B. ovatus might contribute to the enhanced efficacy of anti-PD-1 therapy. Furthermore, metabolomic analysis upon mouse plasma revealed several potential metabolites that upregulated after FMT, including punicic acid and aspirin, might promote the response to anti-PD-1 therapy via their immunomodulatory functions. This work broadens our understanding of the mechanism by which FMT improves the efficacy of anti-PD-1 therapy, which may contribute to the development of novel microbiota-based anti-cancer therapies.

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Host immunomodulatory lipids created by symbionts from dietary amino acids

Cited by 76 publications

References 52 publications

A novel unconventional T cell population enriched in Crohn’s disease

A novel unconventional T cell population enriched in Crohn’s disease

Goat Milk–Derived Lipids Restrain NK T Cell–Dependent Eosinophilic Inflammation in a Murine Model of Atopic Dermatitis

Metagenomic and Metabolomic Analyses Reveal Synergistic Effects of Fecal Microbiota Transplantation and Anti-PD-1 Therapy on Treating Colorectal Cancer

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