ArticleGastroenterology2015
SLAMF4 Is a Negative Regulator of Expansion of Cytotoxic Intraepithelial CD8+ T Cells That Maintains Homeostasis in the Small Intestine.
Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- P2X7R+CD8αβiScience · 2026Article
- SLAMF7 regulates goblet cell mucus production and negatively impacts gut homeostasis and commensalism.Gut microbes · 2025Article
- SLAMF receptors: key regulators of tumor progression and emerging targets for cancer immunotherapy.Molecular cancer · 2025Review
- Imaging of biphasic signalosomes constructed by checkpoint receptor 2B4 in conventional and chimeric antigen receptor-T cells.iScience · 2025Article
- SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy.Frontiers in immunology · 2023Review
- Role of signaling lymphocytic activation molecule family of receptors in the pathogenesis of rheumatoid arthritis: insights and application.Frontiers in pharmacology · 2023Review
- Role of orally induced regulatory T cells in immunotherapy and tolerance.Cellular immunology · 2021Review
- Mechanisms of activation of innate-like intraepithelial T lymphocytes.Mucosal immunology · 2020Review
- CD4CD8αα IELs: They Have Something to Say.Frontiers in immunology · 2019Review
- The elusive case of human intraepithelial T cells in gut homeostasis and inflammation.Nature reviews. Gastroenterology & hepatology · 2018Review
- CXJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Article
- Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice.Frontiers in immunology · 2018Article
- Roles of CD48 in regulating immunity and tolerance.Clinical immunology (Orlando, Fla.) · 2016Review
- Responses to Microbial Challenges by SLAMF Receptors.Frontiers in immunology · 2016Review
- Selective Loss of Signaling Lymphocytic Activation Molecule Family Member 4-Positive CD8+ T Cells Contributes to the Decreased Cytotoxic Cell Activity in Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsIntraepithelial T lymphocyte cells (IEL) are the first immune cells to respond to pathogens; they help maintain the integrity of the epithelial barrier. We studied the function of the mouse glycoprotein Signaling Lymphocyte Activation Molecule Family receptor (SLAMF) 4 (encoded by Slamf4) on the surface of CD8αβ αβ T-cell receptor (TCR)(+) IELs, and the roles of these cells in homeostasis of the small intestine in mice.
methodsSLAMF4(-) CD8(+) αβTCR(+) cells isolated from spleens of OT-I Rag1(-/-) mice were induced to express gut-homing receptors and transferred to C57BL/6J mice; levels of SLAMF4(+) cells were measured in small intestine tissues. After administration of anti-CD3 or antigen, with or without anti-SLAM4, to C57BL/6J and Slamf4(-/-) mice, CD8αβ αβTCR(+) IELs were collected; cytokine production and cytotoxicity were measured. Depletion of CX3CR1(+) phagocytes was assessed in mice by live-cell confocal imaging or by cytofluorometry; small intestine tissues were analyzed by histology and inflammation was quantified.
resultsSplenic CD8(+) αβTCR(+) cells began to express SLAMF4 only after migrating to the small intestine. Injection of C57BL/6J mice with anti-SLAMF4 and anti-CD3 increased levels of interleukin 10 and interferon gamma secretion by IEL, compared with injection of anti-CD3 only. Similarly, the number of granzyme B(+) cytotoxic CD8(+) αβTCR(+) IELs increased in Slamf4(-/-) mice after injection of anti-CD3 and anti-SLAMF4, administration of antigen, or injection of anti-CD3. Surprisingly, in vivo activation of CD8αβ(+) IELs with anti-CD3 or antigen caused transient depletion of CX3CR1(+) phagocytes, which was prolonged by co-injection with anti-SLAMF4 or in Slamf4(-/-) mice. Anti-CD3 aggravated inflammation in the small intestines of Slamf4(-/-) mice and Eat2a(-/-)Eat2b(-/-) mice, indicated by flattened villi and crypt hyperplasia.
conclusionsIn mice, the intestinal environment induces SLAMF4 expression and localization to the surface of CD8(+) αβTCR(+) IELs. Signaling via SLAMF4 controls expansion of cytotoxic CD8αβ(+) IELs, which regulate the reversible depletion of lamina propria phagocytes and inflammation in the small intestine.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.