Single-cell RNA sequencing (scRNA-Seq) provides valuable insights into cell biology. However, current scRNA-Seq analytic approaches do not distinguish between spliced and unspliced mRNA at the level of dimensionality reduction. RNA velocity paradigm suggests that the presence of unspliced mRNA reflects transitional cell states, informative for studies of dynamic processes such as embryogenesis or tissue regeneration. Alternatively, stable cell subsets may also maintain translationally repressed spliced mRNA (e.g., in P-bodies) and/or unspliced mRNA reservoirs for prompt initiation of transcription-independent expression. Thus, functional cell subsets may differ not only in the current levels of actively produced mRNAs, but also in which mRNAs and in what forms are stored in the nucleus and cytoplasm. To enable splicing-aware analysis of scRNA-Seq data, we developed a method called SANSARA (Splicing-Aware scrNa-Seq AppRoAch). We employed SANSARA to characterize peripheral blood regulatory T cell (Treg) subsets, revealing a complementary interplay between the FOXP3 and Helios master transcription factors and high levels of spliced IL10RA, LGALS3, FCRL3, CD38, ITGAL, and LEF1 mRNAs in effector Tregs. Among Th1 and cytotoxic CD4+ T cell subsets, SANSARA also revealed substantial splicing heterogeneity across subset-specific genes. SANSARA is straightforward to implement in current data analysis pipelines and opens new dimensions for scRNA-Seq-based discoveries.

Abu Dhabi Stem Cell Center Al Muntazah United Arab Emirates

Center for Molecular and Cellular Biology Moscow Russia

Central European Institute of Technology Brno Czech Republic

Division of Infection and Immunity Cardiff University School of Medicine University Hospital of Wales Cardiff United Kingdom

Faculty of Bioengineering and Bioinformatics Lomonosov Moscow State University Moscow Russia

Genomics of Adaptive Immunity Department Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry Moscow Russia

Institute of Clinical Molecular Biology Kiel University Kiel Germany

Institute of Translational Medicine Pirogov Russian National Research Medical University Moscow Russia

Systems Immunity Research Institute Cardiff University School of Medicine University Hospital of Wales Cardiff United Kingdom

Zobrazit více v PubMed

Licatalosi DD, Darnell RB. RNA processing and its regulation: global insights into biological networks. Nat Rev Genet. 2010;11(1):75–87. doi: 10.1038/nrg2673 PubMed DOI PMC

Rogalska ME, Vivori C, Valcárcel J. Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects. Nat Rev Genet. 2023;24(4):251–69. doi: 10.1038/s41576-022-00556-8 PubMed DOI

Hsu J, Jarroux J, Joglekar A, Romero JP, Nemec C, Reyes D, et al. Comparing 10x Genomics single-cell 3’ and 5’ assay in short-and long-read sequencing. Cold Spring Harbor Laboratory. 2022. doi: 10.1101/2022.10.27.514084 DOI

Huang Y, Sanguinetti G. BRIE2: computational identification of splicing phenotypes from single-cell transcriptomic experiments. Genome Biol. 2021;22(1):251. doi: 10.1186/s13059-021-02461-5 PubMed DOI PMC

Benegas G, Fischer J, Song YS. Robust and annotation-free analysis of alternative splicing across diverse cell types in mice. Elife. 2022;11:e73520. doi: 10.7554/eLife.73520 PubMed DOI PMC

La Manno G, Soldatov R, Zeisel A, Braun E, Hochgerner H, Petukhov V, et al. RNA velocity of single cells. Nature. 2018;560(7719):494–8. doi: 10.1038/s41586-018-0414-6 PubMed DOI PMC

Pendleton KE, Park S-K, Hunter OV, Bresson SM, Conrad NK. Balance between MAT2A intron detention and splicing is determined cotranscriptionally. RNA. 2018;24(6):778–86. doi: 10.1261/rna.064899.117 PubMed DOI PMC

Gordon JM, Phizicky DV, Neugebauer KM. Nuclear mechanisms of gene expression control: pre-mRNA splicing as a life or death decision. Curr Opin Genet Dev. 2021;67:67–76. doi: 10.1016/j.gde.2020.11.002 PubMed DOI PMC

Krichevsky AM, Kosik KS. Neuronal RNA granules: a link between RNA localization and stimulation-dependent translation. Neuron. 2001;32(4):683–96. doi: 10.1016/s0896-6273(01)00508-6 PubMed DOI

Hubstenberger A, Courel M, Bénard M, Souquere S, Ernoult-Lange M, Chouaib R, et al. P-Body Purification Reveals the Condensation of Repressed mRNA Regulons. Mol Cell. 2017;68(1):144-157.e5. doi: 10.1016/j.molcel.2017.09.003 PubMed DOI

Wolf T, Jin W, Zoppi G, Vogel IA, Akhmedov M, Bleck CKE, et al. Dynamics in protein translation sustaining T cell preparedness. Nat Immunol. 2020;21(8):927–37. doi: 10.1038/s41590-020-0714-5 PubMed DOI PMC

Pessina P, Nevo M, Shi J, Kodali S, Casas E, Cui Y, et al. Selective RNA sequestration in biomolecular condensates directs cell fate transitions. Nature Biotechnology. 2025;Oct 28 (online ahead of print): null. doi: 10.1038/s41587-025-02853-z PubMed DOI PMC

Dumbović G, Braunschweig U, Langner HK, Smallegan M, Biayna J, Hass EP, et al. Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention. Nat Commun. 2021;12(1):3308. doi: 10.1038/s41467-021-23221-w PubMed DOI PMC

Gayoso A, Weiler P, Lotfollahi M, Klein D, Hong J, Streets A, et al. Deep generative modeling of transcriptional dynamics for RNA velocity analysis in single cells. Nat Methods. 2024;21(1):50–9. doi: 10.1038/s41592-023-01994-w PubMed DOI PMC

Lukyanov DK, Kriukova VV, Ladell K, Shagina IA, Staroverov DB, Minasian BE, et al. Repertoire-based mapping and time-tracking of T helper cell subsets in scRNA-Seq. Front Immunol. 2025;16:1536302. doi: 10.3389/fimmu.2025.1536302 PubMed DOI PMC

Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods. 2019;16(12):1289–96. doi: 10.1038/s41592-019-0619-0 PubMed DOI PMC

Tanemoto S, Sujino T, Miyamoto K, Moody J, Yoshimatsu Y, Ando Y, et al. Single-cell transcriptomics of human gut T cells identifies cytotoxic CD4+CD8A+ T cells related to mouse CD4 cytotoxic T cells. Front Immunol. 2022;13:977117. doi: 10.3389/fimmu.2022.977117 PubMed DOI PMC

Dikiy S, Rudensky AY. Principles of regulatory T cell function. Immunity. 2023;56(2):240–55. doi: 10.1016/j.immuni.2023.01.004 PubMed DOI

Sakaguchi S, Mikami N, Wing JB, Tanaka A, Ichiyama K, Ohkura N. Regulatory T Cells and Human Disease. Annu Rev Immunol. 2020;38:541–66. doi: 10.1146/annurev-immunol-042718-041717 PubMed DOI

Yasumizu Y, Takeuchi D, Morimoto R, Takeshima Y, Okuno T, Kinoshita M, et al. Single-cell transcriptome landscape of circulating CD4(+) T cell populations in autoimmune diseases. Cell Genom. 2024;4(2):100473. doi: 10.1016/j.xgen.2023.100473 PubMed DOI PMC

Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4(4):330–6. doi: 10.1038/ni904 PubMed DOI

Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057–61. doi: 10.1126/science.1079490 PubMed DOI

Kim H-J, Barnitz RA, Kreslavsky T, Brown FD, Moffett H, Lemieux ME, et al. Stable inhibitory activity of regulatory T cells requires the transcription factor Helios. Science. 2015;350(6258):334–9. doi: 10.1126/science.aad0616 PubMed DOI PMC

Nakagawa H, Sido JM, Reyes EE, Kiers V, Cantor H, Kim H-J. Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity. Proc Natl Acad Sci U S A. 2016;113(22):6248–53. doi: 10.1073/pnas.1604765113 PubMed DOI PMC

Hsiao W-Y, Lin Y-C, Liao F-H, Chan Y-C, Huang C-Y. Dual-Specificity Phosphatase 4 Regulates STAT5 Protein Stability and Helper T Cell Polarization. PLoS One. 2015;10(12):e0145880. doi: 10.1371/journal.pone.0145880 PubMed DOI PMC

Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H, et al. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol. 2009;10(11):1178–84. doi: 10.1038/ni.1791 PubMed DOI PMC

Chaudhry A, Samstein RM, Treuting P, Liang Y, Pils MC, Heinrich J-M, et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity. 2011;34(4):566–78. doi: 10.1016/j.immuni.2011.03.018 PubMed DOI PMC

Fermino ML, Dias FC, Lopes CD, Souza MA, Cruz ÂK, Liu F-T, et al. Galectin-3 negatively regulates the frequency and function of CD4(+) CD25(+) Foxp3(+) regulatory T cells and influences the course of Leishmania major infection. Eur J Immunol. 2013;43(7):1806–17. doi: 10.1002/eji.201343381 PubMed DOI

Jiang H-R, Al Rasebi Z, Mensah-Brown E, Shahin A, Xu D, Goodyear CS, et al. Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis. J Immunol. 2009;182(2):1167–73. doi: 10.4049/jimmunol.182.2.1167 PubMed DOI

Ocklenburg F, Moharregh-Khiabani D, Geffers R, Janke V, Pfoertner S, Garritsen H, et al. UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells. Lab Invest. 2006;86(7):724–37. doi: 10.1038/labinvest.3700432 PubMed DOI

Agarwal S, Kraus Z, Dement-Brown J, Alabi O, Starost K, Tolnay M. Human Fc Receptor-like 3 Inhibits Regulatory T Cell Function and Binds Secretory IgA. Cell Rep. 2020;30(5):1292-1299.e3. doi: 10.1016/j.celrep.2019.12.099 PubMed DOI

Lyu M, Wang S, Gao K, Wang L, Zhu X, Liu Y, et al. Dissecting the Landscape of Activated CMV-Stimulated CD4+ T Cells in Humans by Linking Single-Cell RNA-Seq With T-Cell Receptor Sequencing. Front Immunol. 2021;12:779961. doi: 10.3389/fimmu.2021.779961 PubMed DOI PMC

Hwang S-H, Jung S-H, Lee S, Choi S, Yoo S-A, Park J-H, et al. Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2015;112(47):E6535-43. doi: 10.1073/pnas.1514152112 PubMed DOI PMC

Nish SA, Zens KD, Kratchmarov R, Lin W-HW, Adams WC, Chen Y-H, et al. CD4+ T cell effector commitment coupled to self-renewal by asymmetric cell divisions. J Exp Med. 2017;214(1):39–47. doi: 10.1084/jem.20161046 PubMed DOI PMC

Liu C, Raab M, Gui Y, Rudd CE. Multi-functional adaptor SKAP1: regulator of integrin activation, the stop-signal, and the proliferation of T cells. Front Immunol. 2023;14:1192838. doi: 10.3389/fimmu.2023.1192838 PubMed DOI PMC

Hoefig KP, Reim A, Gallus C, Wong EH, Behrens G, Conrad C, et al. Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation. Nat Commun. 2021;12(1):5208. doi: 10.1038/s41467-021-25345-5 PubMed DOI PMC

Lee J, Aoki T, Thumkeo D, Siriwach R, Yao C, Narumiya S. T cell-intrinsic prostaglandin E2-EP2/EP4 signaling is critical in pathogenic TH17 cell-driven inflammation. J Allergy Clin Immunol. 2019;143(2):631–43. doi: 10.1016/j.jaci.2018.05.036 PubMed DOI PMC

Hewitson JP, West KA, James KR, Rani GF, Dey N, Romano A, et al. Malat1 Suppresses Immunity to Infection through Promoting Expression of Maf and IL-10 in Th Cells. J Immunol. 2020;204(11):2949–60. doi: 10.4049/jimmunol.1900940 PubMed DOI PMC

Ma X, Cao L, Raneri M, Wang H, Cao Q, Zhao Y, et al. Human HLA-DR+CD27+ regulatory T cells show enhanced antigen-specific suppressive function. JCI Insight. 2023;8(23):e162978. doi: 10.1172/jci.insight.162978 PubMed DOI PMC

Borsellino G, Kleinewietfeld M, Di Mitri D, Sternjak A, Diamantini A, Giometto R, et al. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007;110(4):1225–32. doi: 10.1182/blood-2006-12-064527 PubMed DOI

Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204(6):1257–65. doi: 10.1084/jem.20062512 PubMed DOI PMC

Boison D, Yegutkin GG. Adenosine Metabolism: Emerging Concepts for Cancer Therapy. Cancer Cell. 2019;36(6):582–96. doi: 10.1016/j.ccell.2019.10.007 PubMed DOI PMC

Takenaka MC, Robson S, Quintana FJ. Regulation of the T Cell Response by CD39. Trends Immunol. 2016;37(7):427–39. doi: 10.1016/j.it.2016.04.009 PubMed DOI PMC

Dugast E, Kiss-Toth E, Docherty L, Danger R, Chesneau M, Pichard V, et al. Identification of tribbles-1 as a novel binding partner of Foxp3 in regulatory T cells. J Biol Chem. 2013;288(14):10051–60. doi: 10.1074/jbc.M112.448654 PubMed DOI PMC

Danger R, Dugast E, Braza F, Conchon S, Brouard S. Deciphering the role of TRIB1 in regulatory T-cells. Biochem Soc Trans. 2015;43(5):1075–8. doi: 10.1042/BST20150097 PubMed DOI

Horenstein AL, Chillemi A, Zaccarello G, Bruzzone S, Quarona V, Zito A, et al. A CD38/CD203a/CD73 ectoenzymatic pathway independent of CD39 drives a novel adenosinergic loop in human T lymphocytes. Oncoimmunology. 2013;2(9):e26246. doi: 10.4161/onci.26246 PubMed DOI PMC

Krejcik J, Casneuf T, Nijhof IS, Verbist B, Bald J, Plesner T, et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128(3):384–94. doi: 10.1182/blood-2015-12-687749 PubMed DOI PMC

Klaus T, Wilson AS, Vicari E, Hadaschik E, Klein M, Helbich SSC, et al. Impaired Treg-DC interactions contribute to autoimmunity in leukocyte adhesion deficiency type 1. JCI Insight. 2022;7(24):e162580. doi: 10.1172/jci.insight.162580 PubMed DOI PMC

Wohler J, Bullard D, Schoeb T, Barnum S. LFA-1 is critical for regulatory T cell homeostasis and function. Mol Immunol. 2009;46(11–12):2424–8. doi: 10.1016/j.molimm.2009.04.004 PubMed DOI PMC

Fu W, Ergun A, Lu T, Hill JA, Haxhinasto S, Fassett MS, et al. A multiply redundant genetic switch “locks in” the transcriptional signature of regulatory T cells. Nat Immunol. 2012;13(10):972–80. doi: 10.1038/ni.2420 PubMed DOI PMC

Grossman WJ, Verbsky JW, Barchet W, Colonna M, Atkinson JP, Ley TJ. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity. 2004;21(4):589–601. doi: 10.1016/j.immuni.2004.09.002 PubMed DOI

Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms DR, et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007;27(4):635–46. doi: 10.1016/j.immuni.2007.08.014 PubMed DOI

Salumets A, Tserel L, Kasela S, Limbach M, Milani L, Peterson H, et al. Graves’ disease-associated TSHR gene is demethylated and expressed in human regulatory T cells. Cold Spring Harbor Laboratory. 2022. doi: 10.1101/2022.10.24.513489 DOI

Wu Z, Xi Z, Xiao Y, Zhao X, Li J, Feng N, et al. TSH-TSHR axis promotes tumor immune evasion. J Immunother Cancer. 2022;10(1):e004049. doi: 10.1136/jitc-2021-004049 PubMed DOI PMC

Wu G, Murugesan G, Nagala M, McCraw A, Haslam SM, Dell A, et al. Activation of regulatory T cells triggers specific changes in glycosylation associated with Siglec-1-dependent inflammatory responses. Wellcome Open Res. 2021;6:134. doi: 10.12688/wellcomeopenres.16834.1 PubMed DOI PMC

Sadlon T, Brown CY, Bandara V, Hope CM, Schjenken JE, Pederson SM, et al. Unravelling the molecular basis for regulatory T-cell plasticity and loss of function in disease. Clin Transl Immunology. 2018;7(2):e1011. doi: 10.1002/cti2.1011 PubMed DOI PMC

Cenerenti M, Saillard M, Romero P, Jandus C. The Era of Cytotoxic CD4 T Cells. Front Immunol. 2022;13:867189. doi: 10.3389/fimmu.2022.867189 PubMed DOI PMC

Hashimoto K, Kouno T, Ikawa T, Hayatsu N, Miyajima Y, Yabukami H, et al. Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians. Proc Natl Acad Sci U S A. 2019;116(48):24242–51. doi: 10.1073/pnas.1907883116 PubMed DOI PMC

Wang Y, Chen Z, Wang T, Guo H, Liu Y, Dang N, et al. A novel CD4+ CTL subtype characterized by chemotaxis and inflammation is involved in the pathogenesis of Graves’ orbitopathy. Cell Mol Immunol. 2021;18(3):735–45. doi: 10.1038/s41423-020-00615-2 PubMed DOI PMC

Truong K-L, Schlickeiser S, Vogt K, Boës D, Stanko K, Appelt C, et al. Killer-like receptors and GPR56 progressive expression defines cytokine production of human CD4+ memory T cells. Nat Commun. 2019;10(1):2263. doi: 10.1038/s41467-019-10018-1 PubMed DOI PMC

Patil VS, Madrigal A, Schmiedel BJ, Clarke J, O’Rourke P, de Silva AD, et al. Precursors of human CD4+ cytotoxic T lymphocytes identified by single-cell transcriptome analysis. Sci Immunol. 2018;3(19):eaan8664. doi: 10.1126/sciimmunol.aan8664 PubMed DOI PMC

Opejin A, Surnov A, Misulovin Z, Pherson M, Gross C, Iberg CA, et al. A Two-Step Process of Effector Programming Governs CD4+ T Cell Fate Determination Induced by Antigenic Activation in the Steady State. Cell Rep. 2020;33(8):108424. doi: 10.1016/j.celrep.2020.108424 PubMed DOI PMC

Grenningloh R, Kang BY, Ho I-C. Ets-1, a functional cofactor of T-bet, is essential for Th1 inflammatory responses. J Exp Med. 2005;201(4):615–26. doi: 10.1084/jem.20041330 PubMed DOI PMC

Seo W, Shimizu K, Kojo S, Okeke A, Kohwi-Shigematsu T, Fujii S-I, et al. Runx-mediated regulation of CCL5 via antagonizing two enhancers influences immune cell function and anti-tumor immunity. Nat Commun. 2020;11(1):1562. doi: 10.1038/s41467-020-15375-w PubMed DOI PMC

Swanson BJ, Murakami M, Mitchell TC, Kappler J, Marrack P. RANTES production by memory phenotype T cells is controlled by a posttranscriptional, TCR-dependent process. Immunity. 2002;17(5):605–15. doi: 10.1016/s1074-7613(02)00456-9 PubMed DOI

Elmentaite R, Domínguez Conde C, Yang L, Teichmann SA. Single-cell atlases: shared and tissue-specific cell types across human organs. Nat Rev Genet. 2022;23(7):395–410. doi: 10.1038/s41576-022-00449-w PubMed DOI

Papalexi E, Satija R. Single-cell RNA sequencing to explore immune cell heterogeneity. Nat Rev Immunol. 2018;18(1):35–45. doi: 10.1038/nri.2017.76 PubMed DOI

Liu S, Zhou B, Wu L, Sun Y, Chen J, Liu S. Single-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating T cells. Sci Rep. 2021;11(1):5325. doi: 10.1038/s41598-021-84693-w PubMed DOI PMC

Lei Q, Li C, Zuo Z, Huang C, Cheng H, Zhou R. Evolutionary Insights into RNA trans-Splicing in Vertebrates. Genome Biol Evol. 2016;8(3):562–77. doi: 10.1093/gbe/evw025 PubMed DOI PMC

Sugimoto N, Oida T, Hirota K, Nakamura K, Nomura T, Uchiyama T, et al. Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int Immunol. 2006;18(8):1197–209. doi: 10.1093/intimm/dxl060 PubMed DOI

Seng A, Krausz KL, Pei D, Koestler DC, Fischer RT, Yankee TM, et al. Coexpression of FOXP3 and a Helios isoform enhances the effectiveness of human engineered regulatory T cells. Blood Adv. 2020;4(7):1325–39. doi: 10.1182/bloodadvances.2019000965 PubMed DOI PMC

Zheng GXY, Terry JM, Belgrader P, Ryvkin P, Bent ZW, Wilson R, et al. Massively parallel digital transcriptional profiling of single cells. Nat Commun. 2017;8:14049. doi: 10.1038/ncomms14049 PubMed DOI PMC

Hao Y, Stuart T, Kowalski MH, Choudhary S, Hoffman P, Hartman A, et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat Biotechnol. 2024;42(2):293–304. doi: 10.1038/s41587-023-01767-y PubMed DOI PMC

Maechler M, Rousseeuw P, Struyf A, Hubert M, Hornik K. Cluster analysis basics and extensions. 2025.

Zappia L, Oshlack A. Clustering trees: a visualization for evaluating clusterings at multiple resolutions. Gigascience. 2018;7(7):giy083. doi: 10.1093/gigascience/giy083 PubMed DOI PMC

Pedregosa F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O. Scikit-learn: Machine Learning in Python. Journal of Machine Learning Research. 2011.

Zhang Y, Shang Q, Zhang G. pyDRMetrics - A Python toolkit for dimensionality reduction quality assessment. Heliyon. 2021;7(2):e06199. doi: 10.1016/j.heliyon.2021.e06199 PubMed DOI PMC

Lun A. bluster: Clustering Algorithms for Bioconductor. 2025. doi: 10.18129/B9.bioc.bluster DOI

Blighe K, Rana S, Lewis M. EnhancedVolcano: Publication-ready volcano plots with enhanced colouring and labeling. 2025.

Katagiri T, Kameda H, Nakano H, Yamazaki S. Regulation of T cell differentiation by the AP-1 transcription factor JunB. Immunol Med. 2021;44(3):197–203. doi: 10.1080/25785826.2021.1872838 PubMed DOI

D’Acquisto F. On the adaptive nature of annexin-A1. Curr Opin Pharmacol. 2009;9(4):521–8. doi: 10.1016/j.coph.2009.04.007 PubMed DOI

Huang P, Zhou Y, Liu Z, Zhang P. Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4+ T Cells. Mediators Inflamm. 2016;2016:1701059. doi: 10.1155/2016/1701059 PubMed DOI PMC

Escobar G, Mangani D, Anderson AC. T cell factor 1: A master regulator of the T cell response in disease. Sci Immunol. 2020;5(53):eabb9726. doi: 10.1126/sciimmunol.abb9726 PubMed DOI PMC

Hofland T, Danelli L, Cornish G, Donnarumma T, Hunt DM, de Carvalho LPS, et al. CD4+ T cell memory is impaired by species-specific cytotoxic differentiation, but not by TCF-1 loss. Front Immunol. 2023;14:1168125. doi: 10.3389/fimmu.2023.1168125 PubMed DOI PMC

Srivastava N, Sudan R, Kerr WG. Role of inositol poly-phosphatases and their targets in T cell biology. Front Immunol. 2013;4:288. doi: 10.3389/fimmu.2013.00288 PubMed DOI PMC