Tissue-resident memory T cells (TRM cells) are key elements of tissue immunity. Here, we investigated the role of the regulator of T cell receptor and cytokine signaling, Ptpn2, in the formation and function of TRM cells in skin. Ptpn2-deficient CD8+ T cells displayed a marked defect in generating CD69+ CD103+ TRM cells in response to herpes simplex virus type 1 (HSV-1) skin infection. This was accompanied by a reduction in the proportion of KLRG1- memory precursor cells and a transcriptional bias toward terminal differentiation. Of note, forced expression of KLRG1 was sufficient to impede TRM cell formation. Normalizing memory precursor frequencies by transferring equal numbers of KLRG1- cells restored TRM generation, demonstrating that Ptpn2 impacted skin seeding with precursors rather than downstream TRM cell differentiation. Importantly, Ptpn2-deficient TRM cells augmented skin autoimmunity but also afforded superior protection from HSV-1 infection. Our results emphasize that KLRG1 repression is required for optimal TRM cell formation in skin and reveal an important role of Ptpn2 in regulating TRM cell functionality.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091133 | PMC |
| http://dx.doi.org/10.1084/jem.20200940 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tissue-resident memory T (T) cells are crucial components of the immune system that provide rapid, localized responses to recurrent pathogens at mucosal and epithelial barriers. Unlike circulating memory T cells, T cells are located within peripheral tissues, and they play vital roles in antiviral, antibacterial, and antitumor immunity. Their unique retention and activation mechanisms, including interactions with local epithelial cells and the expression of adhesion molecules, enable their persistence and immediate functionality in diverse tissues.
View Article and Find Full Text PDFCell-Cultured Influenza Vaccine Enhances IFN-γ+ T Cell and Memory T Cell Responses Following A/Victoria/2570/2019 IVR-215 (A/H1N1) Infection.
Vaccines (Basel)
December 2024
The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Annex to Seoul Saint Mary Hospital, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.
Background: Influenza remains a significant public health challenge, with vaccination being a substantial way to prevent it. Cell-cultured influenza vaccines have emerged to improve on the drawbacks of egg-based vaccines, but there are few studies focusing on T cell immunity with both types of vaccines. Therefore, we studied the following 2022-2023 seasonal influenza vaccines with a standard dose and high dose: cell-based (C_sd and C_hd) and egg-based (E_sd and E_hd) vaccines.
View Article and Find Full Text PDFRSV Vaccine with Nanoparticle-Based Poly-Sorbitol Transporter (PST) Adjuvant Improves Respiratory Protection Against RSV Through Inducing Both Systemic and Mucosal Humoral Immunity.
Vaccines (Basel)
November 2024
Department of Systems Biotechnology, Chung-Ang University, Anseong 17456, Republic of Korea.
Respiratory syncytial virus (RSV) causes symptoms similar to a mild cold for adults, but in case of infants, it causes bronchitis and/or pneumonia, and in some cases, mortality. Mucosal immunity within the respiratory tract includes tissue-resident memory T (T) cells and tissue-resident memory B (B) cells, which provides rapid and efficient protection against RSV re-infection. Therefore, vaccine strategies should aim to generate mucosal immune responses.
View Article and Find Full Text PDFTranscription repressor BACH2 redirects short-lived terminally differentiated effector into long-lived memory cells. We postulate that BACH2-mediated long-lived memory programs promote HIV-1 persistence in gut CD4+ T cells. We coupled single-cell DOGMA-seq and TREK-seq to capture chromatin accessibility, transcriptome, surface proteins, T cell receptor, HIV-1 DNA and HIV-1 RNA in 100,744 gut T cells from ten aviremic HIV-1+ individuals and five HIV-1- donors.
View Article and Find Full Text PDFAutogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.
Nat Med
January 2025
Department of Medicine-Medical Oncology, University of Colorado Cancer Center, Denver, CO, USA.
Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!