Kathleen R Bartemes1, Gail M Kephart2, Stephanie J Fox2, Hirohito Kita3. 1. Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minn; Department of Immunology, Mayo Clinic, Rochester, Minn. 2. Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minn. 3. Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minn; Department of Immunology, Mayo Clinic, Rochester, Minn. Electronic address: kita.hirohito@mayo.edu.
Abstract
BACKGROUND: In mice, group 2 innate lymphoid cells (ILC2s) likely mediate helminth immunity, inflammation, and tissue repair and remodeling. However, the involvement of ILC2s in human diseases, such as asthma, is not well understood. OBJECTIVES: The goals of this study were to investigate whether peripheral blood specimens can be used to monitor innate type 2 immunity in human subjects and to examine whether ILC2s are involved in human asthma. METHODS: PBMCs from subjects with allergic asthma (AA), subjects with allergic rhinitis (AR), or healthy control (HC) subjects were cultured in vitro with IL-25 or IL-33. Flow cytometry and cell sorting were used to identify, isolate, and quantitate ILC2s in PBMCs. RESULTS: Human PBMCs produced IL-5 and IL-13 when stimulated with IL-33 or IL-25 in the presence of IL-2 without antigens. In addition, IL-7 or thymic stromal lymphopoietin were able to replace IL-2. The cell population with phenotypic ILC2 characteristics, lineage(-)CD127(+)CRTH2(+) cells, responded to IL-33 and produced large quantities of IL-5 and IL-13 but undetectable levels of IL-4. PBMCs from subjects with AA produced significantly larger amounts of IL-5 and IL-13 in response to IL-25 or IL-33 than from subjects with AR or HC. The prevalence of ILC2s in blood was greater in the AA group than in the AR group or the HC group. CONCLUSIONS: Innate type 2 immune responses are increased in asthma but not in AR, suggesting potential differences in the immunopathogenesis of these diseases. Peripheral blood is useful for evaluating innate type 2 immunity in humans.
BACKGROUND: In mice, group 2 innate lymphoid cells (ILC2s) likely mediate helminth immunity, inflammation, and tissue repair and remodeling. However, the involvement of ILC2s in human diseases, such as asthma, is not well understood. OBJECTIVES: The goals of this study were to investigate whether peripheral blood specimens can be used to monitor innate type 2 immunity in human subjects and to examine whether ILC2s are involved in humanasthma. METHODS: PBMCs from subjects with allergic asthma (AA), subjects with allergic rhinitis (AR), or healthy control (HC) subjects were cultured in vitro with IL-25 or IL-33. Flow cytometry and cell sorting were used to identify, isolate, and quantitate ILC2s in PBMCs. RESULTS:Human PBMCs produced IL-5 and IL-13 when stimulated with IL-33 or IL-25 in the presence of IL-2 without antigens. In addition, IL-7 or thymic stromal lymphopoietin were able to replace IL-2. The cell population with phenotypic ILC2 characteristics, lineage(-)CD127(+)CRTH2(+) cells, responded to IL-33 and produced large quantities of IL-5 and IL-13 but undetectable levels of IL-4. PBMCs from subjects with AA produced significantly larger amounts of IL-5 and IL-13 in response to IL-25 or IL-33 than from subjects with AR or HC. The prevalence of ILC2s in blood was greater in the AA group than in the AR group or the HC group. CONCLUSIONS: Innate type 2 immune responses are increased in asthma but not in AR, suggesting potential differences in the immunopathogenesis of these diseases. Peripheral blood is useful for evaluating innate type 2 immunity in humans.
Authors: Daniel F Gudbjartsson; Unnur S Bjornsdottir; Eva Halapi; Anna Helgadottir; Patrick Sulem; Gudrun M Jonsdottir; Gudmar Thorleifsson; Hafdis Helgadottir; Valgerdur Steinthorsdottir; Hreinn Stefansson; Carolyn Williams; Jennie Hui; John Beilby; Nicole M Warrington; Alan James; Lyle J Palmer; Gerard H Koppelman; Andrea Heinzmann; Marcus Krueger; H Marike Boezen; Amanda Wheatley; Janine Altmuller; Hyoung Doo Shin; Soo-Taek Uh; Hyun Sub Cheong; Brynja Jonsdottir; David Gislason; Choon-Sik Park; Linda M Rasmussen; Celeste Porsbjerg; Jakob W Hansen; Vibeke Backer; Thomas Werge; Christer Janson; Ulla-Britt Jönsson; Maggie C Y Ng; Juliana Chan; Wing Yee So; Ronald Ma; Svati H Shah; Christopher B Granger; Arshed A Quyyumi; Allan I Levey; Viola Vaccarino; Muredach P Reilly; Daniel J Rader; Michael J A Williams; Andre M van Rij; Gregory T Jones; Elisabetta Trabetti; Giovanni Malerba; Pier Franco Pignatti; Attilio Boner; Lydia Pescollderungg; Domenico Girelli; Oliviero Olivieri; Nicola Martinelli; Bjorn R Ludviksson; Dora Ludviksdottir; Gudmundur I Eyjolfsson; David Arnar; Gudmundur Thorgeirsson; Klaus Deichmann; Philip J Thompson; Matthias Wjst; Ian P Hall; Dirkje S Postma; Thorarinn Gislason; Jeffrey Gulcher; Augustine Kong; Ingileif Jonsdottir; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2009-02-08 Impact factor: 38.330
Authors: D S Robinson; Q Hamid; S Ying; A Tsicopoulos; J Barkans; A M Bentley; C Corrigan; S R Durham; A B Kay Journal: N Engl J Med Date: 1992-01-30 Impact factor: 91.245
Authors: G Grünig; M Warnock; A E Wakil; R Venkayya; F Brombacher; D M Rennick; D Sheppard; M Mohrs; D D Donaldson; R M Locksley; D B Corry Journal: Science Date: 1998-12-18 Impact factor: 47.728
Authors: Jesse C Nussbaum; Steven J Van Dyken; Jakob von Moltke; Laurence E Cheng; Alexander Mohapatra; Ari B Molofsky; Emily E Thornton; Matthew F Krummel; Ajay Chawla; Hong-Erh Liang; Richard M Locksley Journal: Nature Date: 2013-09-15 Impact factor: 49.962
Authors: Erin D Gordon; Laura J Simpson; Cydney L Rios; Lando Ringel; Marrah E Lachowicz-Scroggins; Michael C Peters; Agata Wesolowska-Andersen; Jeanmarie R Gonzalez; Hannah J MacLeod; Laura S Christian; Shaopeng Yuan; Liam Barry; Prescott G Woodruff; K Mark Ansel; Karl Nocka; Max A Seibold; John V Fahy Journal: Proc Natl Acad Sci U S A Date: 2016-07-18 Impact factor: 11.205
Authors: Jacqueline-Yvonne Cephus; Matthew T Stier; Hubaida Fuseini; Jeffrey A Yung; Shinji Toki; Melissa H Bloodworth; Weisong Zhou; Kasia Goleniewska; Jian Zhang; Sarah L Garon; Robert G Hamilton; Vasiliy V Poloshukin; Kelli L Boyd; R Stokes Peebles; Dawn C Newcomb Journal: Cell Rep Date: 2017-11-28 Impact factor: 9.423
Authors: Franz Puttur; Laura Denney; Lisa G Gregory; Juho Vuononvirta; Robert Oliver; Lewis J Entwistle; Simone A Walker; Mark B Headley; Ewan J McGhee; James E Pease; Matthew F Krummel; Leo M Carlin; Clare M Lloyd Journal: Sci Immunol Date: 2019-06-07
Authors: Tao Huang; Meredith Hazen; Yonglei Shang; Meijuan Zhou; Xiumin Wu; Donghong Yan; Zhonghua Lin; Margaret Solon; Elizabeth Luis; Hai Ngu; Yongchang Shi; Arna Katewa; David F Choy; Nandhini Ramamoorthi; Erick R Castellanos; Mercedesz Balazs; Min Xu; Wyne P Lee; Marissa L Matsumoto; Jian Payandeh; Joseph R Arron; Jo-Anne Hongo; Jianyong Wang; Isidro Hötzel; Cary D Austin; Karin Reif Journal: JCI Insight Date: 2016-05-19