ArticleImmunity2013
Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation.
Article in Immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 372 papers, 2 of them syntheses that pooled it.
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
372 citing papers in PubMed, 2 syntheses or guidelines pooled it, 558 citations in OpenAlex.
- Pitfalls in complement analysis: A systematic literature review of assessing complement activation.Frontiers in immunology · 2022Pooled it
- Association of complement components with the risk and severity of NAFLD: A systematic review and meta-analysis.Frontiers in immunology · 2022Pooled it
- Complement component C4 regulates amyloid pathology and glial reactivity in mouse model of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
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- Tumor cell-released autophagosome (TRAP) programs inflammatory CAFs to drive the immune-excluded TIME through C3a.Cellular & molecular immunology · 2026Article
- Advances in Complement Research: from Pathophysiology to Precision Medicine.Physiology (Bethesda, Md.) · 2026Review
- Cardiac immunity and heart repair: Mechanism, challenge, and future direction.Chinese medical journal · 2026Review
- What's your name, immune cell?Nature methods · 2026Article
- Local, but not circulating, complement C3 shapes immune checkpoint blockade efficacy by controlling myeloid cell infiltration.Nature communications · 2026Article
- Tumor-Derived Complement C3 Overexpression in STK11-Mutant Lung Adenocarcinoma Drives Tumor Growth and Immune Checkpoint Inhibitor Resistance.Cancer immunology research · 2026Article
- Mitochondria: The Crossroads of Complement Activation and Kidney Injury Progression.International journal of molecular sciences · 2026Review
- Novel interactions between the C5-C5aR1 Axis and IF1: Implications for kidney mitochondrial physiology and ischemia-reperfusion injury.Physiological reports · 2026Article
- Analysis of the Recovery of Immune Status in the Patients With Paroxysmal Nocturnal Hemoglobinuria After Treatment With C5 Complement Inhibitor.Journal of clinical laboratory analysis · 2026Article
- Mechanistic insight into complement C3 regulation during chronic HBV infection: effect on viral persistence and host immune response.Journal of biomedical science · 2026Article
- Adventitial Niches, Complement and Inflammation in Pulmonary Vascular Disease: Current Status and Future Directions.Comprehensive Physiology · 2026Review
- C/EBP-β-regulated complement hyperactivation in spleen of SFTSV-infected mice: A clue to targeted complement therapy.PLoS pathogens · 2026Article
- Longitudinal investigation of the T helper (Th)1-Th2 balance and complement system in clinical high risk for psychosis cohort.Translational psychiatry · 2026Article
- Identification of novel blood-borne soluble binding partners of factor H-related proteins.Scientific reports · 2026Article
- Complement system in cancer: friend or foe of immunotherapy.Journal for immunotherapy of cancer · 2026Review
312 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 10 institutions in 6 countries.
Funding
Abstract
Complement is viewed as a critical serum-operative component of innate immunity, with processing of its key component, C3, into activation fragments C3a and C3b confined to the extracellular space. We report here that C3 activation also occurred intracellularly. We found that the T cell-expressed protease cathepsin L (CTSL) processed C3 into biologically active C3a and C3b. Resting T cells contained stores of endosomal and lysosomal C3 and CTSL and substantial amounts of CTSL-generated C3a. While "tonic" intracellular C3a generation was required for homeostatic T cell survival, shuttling of this intracellular C3-activation-system to the cell surface upon T cell stimulation induced autocrine proinflammatory cytokine production. Furthermore, T cells from patients with autoimmune arthritis demonstrated hyperactive intracellular complement activation and interferon-γ production and CTSL inhibition corrected this deregulated phenotype. Importantly, intracellular C3a was observed in all examined cell populations, suggesting that intracellular complement activation might be of broad physiological significance.
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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.