Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa
Summary: The Btla inhibitory receptor limits innate and adaptive immune responses, both preventing the development of autoimmune disease and restraining anti-viral and anti-tumor responses. It remains unclear how the functions of Btla in diverse lymphocytes contribute to immunoregulation. Here, we s...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124722002972 |
| _version_ | 1818317840854286336 |
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| author | Caroline Stienne Richard Virgen-Slane Lisa Elmén Marisol Veny Sarah Huang Jennifer Nguyen Elizabeth Chappell Mary Olivia Balmert Jr-Wen Shui Michelle A. Hurchla Mitchell Kronenberg Scott N. Peterson Kenneth M. Murphy Carl F. Ware John R. Šedý |
| author_facet | Caroline Stienne Richard Virgen-Slane Lisa Elmén Marisol Veny Sarah Huang Jennifer Nguyen Elizabeth Chappell Mary Olivia Balmert Jr-Wen Shui Michelle A. Hurchla Mitchell Kronenberg Scott N. Peterson Kenneth M. Murphy Carl F. Ware John R. Šedý |
| author_sort | Caroline Stienne |
| collection | DOAJ |
| description | Summary: The Btla inhibitory receptor limits innate and adaptive immune responses, both preventing the development of autoimmune disease and restraining anti-viral and anti-tumor responses. It remains unclear how the functions of Btla in diverse lymphocytes contribute to immunoregulation. Here, we show that Btla inhibits activation of genes regulating metabolism and cytokine signaling, including Il6 and Hif1a, indicating a regulatory role in humoral immunity. Within mucosal Peyer's patches, we find T-cell-expressed Btla-regulated Tfh cells, while Btla in T or B cells regulates GC B cell numbers. Treg-expressed Btla is required for cell-intrinsic Treg homeostasis that subsequently controls GC B cells. Loss of Btla in lymphocytes results in increased IgA bound to intestinal bacteria, correlating with altered microbial homeostasis and elevations in commensal and pathogenic bacteria. Together our studies provide important insights into how Btla functions as a checkpoint in diverse conventional and regulatory lymphocyte subsets to influence systemic immune responses. |
| first_indexed | 2024-12-13T09:43:43Z |
| format | Article |
| id | doaj.art-1478349ce0de43279023cb936638d0d8 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T09:43:43Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1478349ce0de43279023cb936638d0d82022-12-21T23:52:08ZengElsevierCell Reports2211-12472022-03-013812110553Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosaCaroline Stienne0Richard Virgen-Slane1Lisa Elmén2Marisol Veny3Sarah Huang4Jennifer Nguyen5Elizabeth Chappell6Mary Olivia Balmert7Jr-Wen Shui8Michelle A. Hurchla9Mitchell Kronenberg10Scott N. Peterson11Kenneth M. Murphy12Carl F. Ware13John R. Šedý14Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAImmunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USATumor Microenvironment and Cancer Immunology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAImmunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAImmunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAImmunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAImmunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAImmunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USALa Jolla Institute for Immunology, La Jolla, CA 92037, USADepartment of Pathology and Immunology, Washington University in Saint Louis School of Medicine, Saint Louis, MO 63110, USALa Jolla Institute for Immunology, La Jolla, CA 92037, USATumor Microenvironment and Cancer Immunology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USADepartment of Pathology and Immunology, Washington University in Saint Louis School of Medicine, Saint Louis, MO 63110, USAImmunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Corresponding authorImmunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Corresponding authorSummary: The Btla inhibitory receptor limits innate and adaptive immune responses, both preventing the development of autoimmune disease and restraining anti-viral and anti-tumor responses. It remains unclear how the functions of Btla in diverse lymphocytes contribute to immunoregulation. Here, we show that Btla inhibits activation of genes regulating metabolism and cytokine signaling, including Il6 and Hif1a, indicating a regulatory role in humoral immunity. Within mucosal Peyer's patches, we find T-cell-expressed Btla-regulated Tfh cells, while Btla in T or B cells regulates GC B cell numbers. Treg-expressed Btla is required for cell-intrinsic Treg homeostasis that subsequently controls GC B cells. Loss of Btla in lymphocytes results in increased IgA bound to intestinal bacteria, correlating with altered microbial homeostasis and elevations in commensal and pathogenic bacteria. Together our studies provide important insights into how Btla functions as a checkpoint in diverse conventional and regulatory lymphocyte subsets to influence systemic immune responses.http://www.sciencedirect.com/science/article/pii/S2211124722002972CP: ImmunologyCP: Microbiology |
| spellingShingle | Caroline Stienne Richard Virgen-Slane Lisa Elmén Marisol Veny Sarah Huang Jennifer Nguyen Elizabeth Chappell Mary Olivia Balmert Jr-Wen Shui Michelle A. Hurchla Mitchell Kronenberg Scott N. Peterson Kenneth M. Murphy Carl F. Ware John R. Šedý Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa Cell Reports CP: Immunology CP: Microbiology |
| title | Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa |
| title_full | Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa |
| title_fullStr | Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa |
| title_full_unstemmed | Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa |
| title_short | Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa |
| title_sort | btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124722002972 |
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