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                                             published a study showing that a    would be that we’d have a drug
                                     6       sugar-lipid molecule released by    that can modulate inflammation in
                                             B. fragilis had anti-inflammatory   the colon and beyond.”
        The Harvard team’s experiments       effects on the gut and protected
        revealed that synthetic, lab-made    mice from colitis, but the scientists   Co-authors included T. Praveena,
        branched-chain lipid molecules       did not know how these molecules    Heebum Song, Ji-Sun Yoo, Da-
        induced NK T cells to release        were made by the microbe, nor the   Jung Jung, Deniz Erturk-Hasdemir,
        the immune-signaling chemical        specific structural features of the   Yoon Soo Hwang, ChangWon
        IL-2, whereas the lab-made           sugar-lipids that conferred the anti-  Lee, Jérôme Le Nours, Hyunsoo
        straight-chained versions of these   inflammatory effect. The current    Kim, Jesang Lee, and Richard
        molecules did not. Thus activated,   study answers this question         Blumberg.
        the NK T cells, in turn, induced the   demonstrating that the sugar-lipid
        expression of genes that regulate    molecules made by this particular   The work was supported by
        immunity but not of genes that       organism are branched-chain         National Institutes of Health
        drive inflammation.                  and it is precisely that branched-  grants K01-DK102771, R01-
                                             chain structure that allows them    AT010268, and R01-DK044319;
        Using a structural biology           to bind to immune cells in a        by Department of Defense
        approach, Jamie Rossjohn,            way that dampens these cells’       grant W81XWH-19-1-0625; by
        professor of biochemistry and        proinflammatory signaling.          Brigham and Women’s Hospital
        molecular biology at Monash                                              Department of Anesthesiology,
        Biomedicine Discovery Institute in   “Our new work demonstrates that     Perioperative and Pain Medicine
        Australia, elucidated how the lipid   the branching of the lipid structure   Basic Science Grant; by the
        structure engages with and binds     induces a very different response   National Research Foundation of
        to antigen presenting cells -- the   -- the branching in the structure   Korea grants 2014R1A3A2030423
        immune cells that give NK T cells    induces an anti-inflammatory        and 2012M3A9C404878; and by
        the go-ahead to produce anti-        rather than a proinflammatory       the Australian Research Council
        inflammatory chemicals.              response,” Kasper said.             grant CE140100011 and Australian
                                                                                 Research Council Laureate
        In a final step, the researchers     The findings offer hope             Fellowship and Future Fellowships.
        treated mice with ulcerative colitis   that inflammatory diseases
        with the branched-chain sugar-lipid   mediated by these NK T cells       Relevant disclosures
        molecule. Animals that received      could one day be treated
        treatment with the branched-         with inflammation-dampening         Oh, Blumberg, and
        chain molecule fared much better     microbial molecules made in the     Kasper have filed a patent
        than untreated animals. They         lab, the researchers said.          for Bacteroides fragilis
        not only gained weight, but when                                         α-galactosylceramides(BfaGCs)
        researchers examined the gut cells   The exact function of NK T cells --   and related structures. Oh, Park,
        of the mice under a microscope,      the immune cells that the microbe-  and Kasper have filed a patent
        they observed that these cells       made molecule ultimately activates   on the functions of BfaGCs and
        also had minimal signs of colon      to control colonic inflammation     related structures.
        inflammation.                        in mice -- is not well-understood,
                                             Kasper said. However, given         Story Source:
        Taken together, the experiments      that these cells line the human     Materials provided by Harvard
        provide a structural and molecular   gastrointestinal tract and the lungs   Medical School. Original written by
        explanation of previously observed   and are also found in the liver and   Ekaterina Pesheva. Note: Content
        anti-inflammatory effects of this    spleen, they likely play a significant   may be edited for style and length.
        class of sugar-lipids produced by    role in immune regulation. Previous
        the gut microbe B. fragilis.         research points to these cells’     Journal Reference:
                                             likely involvement in a range of    1. Sungwhan F. Oh, T. Praveena,
        “This work offers a great example    inflammatory conditions, including   Heebum Song, Ji-Sun Yoo, Da-
        of transdisciplinary discovery-      ulcerative colitis, and to a possible   Jung Jung, Deniz Erturk-Hasdemir,
        based research aimed at              role in airway inflammatory         Yoon Soo Hwang, ChangWon C.
        answering a major question in        conditions such as asthma.          Lee, Jérôme Le Nours, Hyunsoo
        biomedical sciences, namely,                                             Kim, Jesang Lee, Richard S.
        how the immune system can            “We can never isolate enough        Blumberg, Jamie Rossjohn, Seung
        be modulated by the interplay        of these immune-modulatory          Bum Park, Dennis L. Kasper. Host
        between diet and the microbiota,”    molecules from bacteria for         immunomodulatory lipids created
        Rossjohn said.                       therapeutic use, but the beauty of   by symbionts from dietary amino
                                             this is now we can synthesize them   acids. Nature, 2021; DOI: 10.1038/
        In 2014, Kasper and colleagues       in the lab,” Kasper said. “The idea   s41586-021-04083-0


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