ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Smad4 promotes differentiation of effector and circulating memory CD8 T cells but is dispensable for tissue-resident memory CD8 T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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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.
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Who cites it
44 citing papers in PubMed, 56 citations in OpenAlex.
- Impact of etonogestrel implant use on T-cell and cytokine profiles in the female genital tract and blood.PloS one · 2020Trial
- SKI is critical to counter TGF-β signaling to promote T cell function and autoimmunity.Science advances · 2026Article
- Smad4 and Eomes converge on a shared transcriptional program associated with inflammatory CD8 T-cell differentiation.Frontiers in immunology · 2026Article
- T-bet deficiency and Hic1 induction override TGF-β-dependency in the formation of CD103Cell reports · 2024Article
- SMAD4 enhances the cytotoxic efficacy of human NK cells against colorectal cancer cells via the mFrontiers in immunology · 2024Article
- TGFβ control of immune responses in cancer: a holistic immuno-oncology perspective.Nature reviews. Immunology · 2023Review
- Unique properties of tissue-resident memory T cells in the lungs: implications for COVID-19 and other respiratory diseases.Nature reviews. Immunology · 2023Review
- Extracorporeal photopheresis as an immunomodulatory treatment modality for chronic GvHD and the importance of emerging biomarkers.Frontiers in immunology · 2023Review
- The diverse effects of transforming growth factor-β and SMAD signaling pathways during the CTL response.Frontiers in immunology · 2023Review
- The effect of SMAD4 on the prognosis and immune response in hypopharyngeal carcinoma.Frontiers in medicine · 2023Article
- CTLs Get SMAD When Pathogens Tell Them Where to Go.Journal of immunology (Baltimore, Md. : 1950) · 2022Review
- SMAD4 and TGFβ are architects of inverse genetic programs during fate determination of antiviral CTLs.eLife · 2022Article
- SMAD4, activated by the TCR-triggered MEK/ERK signaling pathway, critically regulates CD8Science advances · 2022Article
- Lymphoid tissue residency: A key to understand Tcf-1Frontiers in immunology · 2022Review
- Overcoming TGFβ-mediated immune evasion in cancer.Nature reviews. Cancer · 2022Review
- CD20 positive CD8 T cells are a unique and transcriptionally-distinct subset of T cells with distinct transmigration properties.Scientific reports · 2021Article
- Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity.Nature immunology · 2021Article
- Article
- Interplay of Inflammatory, Antigen and Tissue-Derived Signals in the Development of Resident CD8 Memory T Cells.Frontiers in immunology · 2021Review
- Age-Related Dynamics of Lung-Resident Memory CD8Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Tissue-resident memory CD8 T cells are a unique subset of virus-specific CTLs that bolster local immune responses after becoming lodged in previously infected tissues. These cells provide enhanced protection by intercepting returning pathogens before a new infection gets established. In contrast, central memory CD8 T cells circulate in the bloodstream and proliferate in secondary lymphoid organs before replenishing effector and memory CD8 T cell populations in remote parts of the body. Both populations of virus-specific memory CD8 T cells participate in immunity to influenza virus infection; however, the signaling pathways that instruct developing memory CD8 T cells to distribute to specific tissues are poorly defined. We show that TGF-β promotes the development of pulmonary tissue-resident memory T cells via a signaling pathway that does not require the downstream signaling intermediate Sma- and Mad-related protein (Smad)4. In contrast, circulating memory CD8 T cells have no requirement for TGF-β but show signs of arrested development in the absence of Smad4, including aberrant CD103 expression. These signaling pathways alter the distribution of virus-specific CTLs in the lungs but do not prevent robust cytokine responses. Our data show that Smad4 is required for normal differentiation of multiple subsets of virus-specific CD8 T cells. In normal circumstances, Smad4 may be activated via a pathway that bypasses the TGF-β receptor. Improved understanding of these signaling pathways could be used to augment vaccine-induced immunity.
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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.