Journal article
Interleukin-33 activates regulatory T cells to suppress innate gamma delta T cell responses in the lung
Nature immunology, Vol.21(11), p.1371
11/01/2020
DOI: 10.1038/s41590-020-0785-3
PMCID: PMC7578082
PMID: 32989331
Abstract
Foxp3(+)regulatory T (T-reg) cells expressing the interleukin (IL)-33 receptor ST2 mediate tissue repair in response to IL-33. Whether T(reg)cells also respond to the alarmin IL-33 to regulate specific aspects of the immune response is not known. Here we describe an unexpected function of ST2(+)T(reg)cells in suppressing the innate immune response in the lung to environmental allergens without altering the adaptive immune response. Following allergen exposure, ST2(+)T(reg)cells were activated by IL-33 to suppress IL-17-producing gamma delta T cells. ST2 signaling in T(reg)cells induced Ebi3, a component of the heterodimeric cytokine IL-35 that was required for T(reg)cell-mediated suppression of gamma delta T cells. This response resulted in fewer eosinophil-attracting chemokines and reduced eosinophil recruitment into the lung, which was beneficial to the host in reducing allergen-induced inflammation. Thus, we define a fundamental role for ST2(+)T(reg)cells in the lung as a negative regulator of the early innate gamma delta T cell response to mucosal injury.
Luster and colleagues show that T(reg)cells that reside in lung mucosa can respond to IL-33 upon allergen exposure and suppress innate cell responses. IL-33-activated ST2(+)T(reg)cells secrete IL-35, which suppresses IL-17 production by gamma delta T cells and lessens eosinophil recruitment into the lung.
Details
- Title: Subtitle
- Interleukin-33 activates regulatory T cells to suppress innate gamma delta T cell responses in the lung
- Creators
- Lucas D. Faustino - Massachusetts General HospitalJason W. Griffith - Massachusetts General HospitalRod A. Rahimi - Massachusetts General HospitalKeshav Nepal - Massachusetts General HospitalDaniel L. Hamilos - Massachusetts General HospitalJosalyn L. Cho - Massachusetts General HospitalBenjamin D. Medoff - Massachusetts General HospitalJames J. Moon - Massachusetts General HospitalDario A. A. Vignali - University of PittsburghAndrew D. Luster - Massachusetts General Hospital
- Resource Type
- Journal article
- Publication Details
- Nature immunology, Vol.21(11), p.1371
- DOI
- 10.1038/s41590-020-0785-3
- PMID
- 32989331
- PMCID
- PMC7578082
- NLM abbreviation
- Nat Immunol
- ISSN
- 1529-2908
- eISSN
- 1529-2916
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 28
- Grant note
- R01AI040618; U19AI095261; T32HL116275; K08AI125816; K08 HL140173; R01CA203689 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 237062/2012-7 / National Council of Scientific Development and Technology
- Language
- English
- Date published
- 11/01/2020
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984359905002771
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