Natural Tr1-like cells do not confer long-term tolerogenic memory
IL-10-producing Tr1 cells promote tolerance but their contributions to tolerogenic memory are unclear. Using 10BiT mice that carry a Foxp3-eGFP reporter and stably express CD90.1 following IL-10 production, we characterized the spatiotemporal dynamics of Tr1 cells in a house dust mite model of aller...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2019-10-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/44821 |
| _version_ | 1811199456307052544 |
|---|---|
| author | Koshika Yadava Carlos Obed Medina Heather Ishak Irina Gurevich Hedwich Kuipers Elya Ali Shamskhou Ievgen O Koliesnik James J Moon Casey Weaver Kari Christine Nadeau Paul L Bollyky |
| author_facet | Koshika Yadava Carlos Obed Medina Heather Ishak Irina Gurevich Hedwich Kuipers Elya Ali Shamskhou Ievgen O Koliesnik James J Moon Casey Weaver Kari Christine Nadeau Paul L Bollyky |
| author_sort | Koshika Yadava |
| collection | DOAJ |
| description | IL-10-producing Tr1 cells promote tolerance but their contributions to tolerogenic memory are unclear. Using 10BiT mice that carry a Foxp3-eGFP reporter and stably express CD90.1 following IL-10 production, we characterized the spatiotemporal dynamics of Tr1 cells in a house dust mite model of allergic airway inflammation. CD90.1+Foxp3-IL-10+ Tr1 cells arise from memory cells and rejoin the tissue-resident memory T-cell pool after cessation of IL-10 production. Persistent antigenic stimulation is necessary to sustain IL-10 production and Irf1 and Batf expression distinguishes CD90.1+Foxp3-IL-10+ Tr1 cells from CD90.1+Foxp3-IL-10- ‘former’ Tr1. Depletion of Tr1-like cells after primary sensitization exacerbates allergic airway inflammation. However, neither transfer nor depletion of former Tr1 cells influences either Tr1 numbers or the inflammatory response during subsequent allergen memory re-challenge weeks later. Together these data suggest that naturally-arising Tr1 cells do not necessarily give rise to more Tr1 upon allergen re-challenge or contribute to tolerogenic memory. This phenotypic instability may limit efforts to re-establish tolerance by expanding Tr1 in vivo. |
| first_indexed | 2024-04-12T01:49:30Z |
| format | Article |
| id | doaj.art-8b7fcf2e0605494491f31295417f4c06 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:49:30Z |
| publishDate | 2019-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8b7fcf2e0605494491f31295417f4c062022-12-22T03:52:59ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.44821Natural Tr1-like cells do not confer long-term tolerogenic memoryKoshika Yadava0https://orcid.org/0000-0002-5827-9177Carlos Obed Medina1https://orcid.org/0000-0002-8324-7994Heather Ishak2Irina Gurevich3Hedwich Kuipers4Elya Ali Shamskhou5Ievgen O Koliesnik6James J Moon7https://orcid.org/0000-0001-8246-931XCasey Weaver8Kari Christine Nadeau9Paul L Bollyky10https://orcid.org/0000-0003-2499-9448Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Beckman Center, Stanford University School of Medicine, Stanford, United States; Radcliffe Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Beckman Center, Stanford University School of Medicine, Stanford, United StatesDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Beckman Center, Stanford University School of Medicine, Stanford, United StatesDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Beckman Center, Stanford University School of Medicine, Stanford, United StatesDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Beckman Center, Stanford University School of Medicine, Stanford, United States; Department of Clinical Neurosciences, University of Calgary, Calgary, CanadaDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Beckman Center, Stanford University School of Medicine, Stanford, United StatesDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Beckman Center, Stanford University School of Medicine, Stanford, United StatesCenter for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, United States; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, United StatesBevill Biomedical Research Building, The University of Alabama at Birmingham, Birmingham, United StatesSean N Parker Center for Allergy & Asthma Research, Stanford University, Mountain View, United StatesDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Beckman Center, Stanford University School of Medicine, Stanford, United StatesIL-10-producing Tr1 cells promote tolerance but their contributions to tolerogenic memory are unclear. Using 10BiT mice that carry a Foxp3-eGFP reporter and stably express CD90.1 following IL-10 production, we characterized the spatiotemporal dynamics of Tr1 cells in a house dust mite model of allergic airway inflammation. CD90.1+Foxp3-IL-10+ Tr1 cells arise from memory cells and rejoin the tissue-resident memory T-cell pool after cessation of IL-10 production. Persistent antigenic stimulation is necessary to sustain IL-10 production and Irf1 and Batf expression distinguishes CD90.1+Foxp3-IL-10+ Tr1 cells from CD90.1+Foxp3-IL-10- ‘former’ Tr1. Depletion of Tr1-like cells after primary sensitization exacerbates allergic airway inflammation. However, neither transfer nor depletion of former Tr1 cells influences either Tr1 numbers or the inflammatory response during subsequent allergen memory re-challenge weeks later. Together these data suggest that naturally-arising Tr1 cells do not necessarily give rise to more Tr1 upon allergen re-challenge or contribute to tolerogenic memory. This phenotypic instability may limit efforts to re-establish tolerance by expanding Tr1 in vivo.https://elifesciences.org/articles/44821IL-10TR1allergymemoryhouse dust mite |
| spellingShingle | Koshika Yadava Carlos Obed Medina Heather Ishak Irina Gurevich Hedwich Kuipers Elya Ali Shamskhou Ievgen O Koliesnik James J Moon Casey Weaver Kari Christine Nadeau Paul L Bollyky Natural Tr1-like cells do not confer long-term tolerogenic memory eLife IL-10 TR1 allergy memory house dust mite |
| title | Natural Tr1-like cells do not confer long-term tolerogenic memory |
| title_full | Natural Tr1-like cells do not confer long-term tolerogenic memory |
| title_fullStr | Natural Tr1-like cells do not confer long-term tolerogenic memory |
| title_full_unstemmed | Natural Tr1-like cells do not confer long-term tolerogenic memory |
| title_short | Natural Tr1-like cells do not confer long-term tolerogenic memory |
| title_sort | natural tr1 like cells do not confer long term tolerogenic memory |
| topic | IL-10 TR1 allergy memory house dust mite |
| url | https://elifesciences.org/articles/44821 |
| work_keys_str_mv | AT koshikayadava naturaltr1likecellsdonotconferlongtermtolerogenicmemory AT carlosobedmedina naturaltr1likecellsdonotconferlongtermtolerogenicmemory AT heatherishak naturaltr1likecellsdonotconferlongtermtolerogenicmemory AT irinagurevich naturaltr1likecellsdonotconferlongtermtolerogenicmemory AT hedwichkuipers naturaltr1likecellsdonotconferlongtermtolerogenicmemory AT elyaalishamskhou naturaltr1likecellsdonotconferlongtermtolerogenicmemory AT ievgenokoliesnik naturaltr1likecellsdonotconferlongtermtolerogenicmemory AT jamesjmoon naturaltr1likecellsdonotconferlongtermtolerogenicmemory AT caseyweaver naturaltr1likecellsdonotconferlongtermtolerogenicmemory AT karichristinenadeau naturaltr1likecellsdonotconferlongtermtolerogenicmemory AT paullbollyky naturaltr1likecellsdonotconferlongtermtolerogenicmemory |