David Artis, PhD
The goals of the Artis lab are to understand the regulatory mechanisms that control immune cell homeostasis at the body's barrier surfaces. Employing diverse models of microbial colonization, pathogen infection and chronic inflammation, research in the Artis lab is examining how mammalian host genetics and signals derived from commensal microbial communities influence innate and adaptive immune responses in the skin, lung and intestine.
Ongoing studies are examining the influence of host genetic- and environmental-derived signals on the development and functions of innate and adaptive immune cells in the context of health and disease. The findings of these studies offer the potential to identify new therapeutic targets to limit infection, chronic inflammation and autoimmune diseases.
The immune system at mucosal sites must be tightly regulated to mediate rapid immunity to invading pathogens, while limiting over-reactive responses that drive chronic inflammation. In particular, type 2 immune responses in the airway or gastrointestinal tract are essential to protect from helminth parasites, but if dysregulated, drive asthma and allergic inflammation. Despite this knowledge, we do not yet fully appreciate the complexity of cellular and molecular signals that control these responses, which will be critical for developing the next generation of preventative, therapeutic or curative treatments. The fundamental focus of this renewal application for the Mucosal Immunology Studies Team is to define novel pathways by which the type 2 immune response harnesses signals associated with the nervous system to regulate rapid mucosal immunity and inflammation. In this context, we will define: (i) the pathways that induce and regulate these neuronal signals, (ii) the functional significance of these pathways in type 2 mucosal immunity and inflammation, and (iii) whether it is possible to therapeutically target these signals to boost immunity to helminth infection or reduced chronic allergic inflammation. We will employ innovative approaches and develop new tools to address these fundamental gaps in knowledge, and where possible, translate our findings from mice into humans. Results from these studies will significantly advance our understanding of the pathways that are essential to mediate rapid immunity and inflammation at mucosal sites and could provoke the next generation of preventative, therapeutic and curative treatment strategies.
Current Grant Support
Research in the Artis lab is supported by the National Institutes of Health (DK126871, AI151599, AI095466, AI095608, AR070116, AI172027, DK132244 all to D.A.), the Crohn's and Colitis Foundation, CURE for IBD, the Sanders Family Foundation, the Rosanne H. Silbermann Foundation and the WCM Jill Roberts Institute for Research in IBD.
David Artis, PhD
Arifuzzaman M, Won TH, Li TT, Yano H, Digumarthi S, Heras AF, Zhang W, Parkhurst CN, Kashyap S, Jin WB, Putzel GG, Tsou AM, Chu C, Wei Q, Grier A, JRI IBD Live Cell Bank Consortium, Worgall S, Guo CJ, Schroeder FC, Artis D. Inulin fiber promotes microbiota-derived bile acids and type 2 inflammation. Nature 2022 Nov;611(7936):578-584. doi: 10.1038/s41586-022-05380-y. Epub 2022 Nov 2. PMID: 36323778.
Tsou AM, Yano H, Parkhurst CN1, Mahlakõiv T, Chu C, Zhang W, He Z, Jarick KJ, Zhong C, Putzel GG, Hatazaki M, JRI IBD Live Cell Bank Consortium, Lorenz IC, Andrew D, Balderes P, Klose CSN, Lira SA, Artis D. Neuropeptide regulation of non-redundant ILC2 responses at barrier surfaces. Nature 2022 Nov;611(7937):787-793. doi: 10.1038/s41586-022-05297-6. Epub 2022 Nov 2. PMID: 36323781.
Zhang W, Lyu M, Bessman NJ, Xie Z, Arifuzzaman M, Yano H, Parkhurst CN, Chu C, Zhou L, Putzel GG, Li TT, Jin WB, Zhou J, JRI Live Cell Bank, Hu H, Tsou AM, Guo CJ, Artis D. Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection. Cell 2022 Oct 27;185(22):4170-4189.e20. doi: 10.1016/j.cell.2022.09.008. Epub 2022 Oct 14. PMID: 36240781.
Chu C, Parkhurst CN, Zhang W, Zhou L, Yano H, Arifuzzaman M, Artis D. The ChAT-acetylcholine pathway promotes group 2 innate lymphoid cell responses and anti-helminth immunity. Sci Immunol. 2021 Mar 5;6(57):eabe3218. doi: 10.1126/sciimmunol.abe3218. PMID: 33674322
Chung H, Parkhurst CN, Magee EM, Phillips D, Habibi E, Chen F, Yeung BZ, Waldman J, Artis D, Regev A. Joint single-cell measurements of nuclear proteins and RNA in vivo. Nat Methods. 2021 Oct;18(10):1204-1212. doi: 10.1038/s41592-021-01278-1. Epub 2021 Oct 4. PMID: 34608310
Kabata H, Flamar AL, Mahlakõiv T, Moriyama S, Rodewald HR, Ziegler SF, Artis D. Targeted deletion of the TSLP receptor reveals cellular mechanisms that promote type 2 airway inflammation. Mucosal Immunol. 2020 Jul;13(4):626-636. doi: 10.1038/s41385-020-0266-x. Epub 2020 Feb 17. PMID: 32066836
Flamar AL, Klose CSN, Moeller JB, Mahlakõiv T, Bessman NJ, Zhang W, Moriyama S, Stokic-Trtica V, Rankin LC, Putzel GG, Rodewald HR, He Z, Chen L, Lira SA, Karsenty G, Artis D. Interleukin-33 Induces the Enzyme Tryptophan Hydroxylase 1 to Promote Inflammatory Group 2 Innate Lymphoid Cell-Mediated Immunity. Immunity. 2020 Apr 14;52(4):606-619.e6. doi: 10.1016/j.immuni.2020.02.009. Epub 2020 Mar 10. PMID: 32160524.
Monticelli LA, Diamond JM, Saenz SA, Tait Wojno ED, Porteous MK, Cantu E, Artis, D, Christie JD. Innate Lymphoid Cell Composition Is Altered in Primary Graft Dysfunction. Am J Respir Crit Care Med. 2020 Jan 1;201(1):63-72. doi: 10.1164/rccm.201906-1113OC. PMID: 31394048
Klose CSN, Artis D. Innate lymphoid cells control signaling circuits to regulate tissue-specific immunity. Cell Res. 2020 Jun; 30(6): 475 -491. Doi: 10.1038/s41422-020-0323-8. Epub 2020 May 6. PMID: 32376911.
Chu C, Artis D, Chiu IM. Neuro-immune Interactions in the Tissues. Immunity. 2020 Mar 17;52(3):464-474. doi: 10.1016/j.immuni.2020.02.017.PMID: 32187517.