ArticleImmunity2021
The tissue protective functions of interleukin-22 can be decoupled from pro-inflammatory actions through structure-based design.
Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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
36 citing papers in PubMed, 64 citations in OpenAlex.
- Article
- Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026Review
- Cytokine multimerization: when more is more and sometimes less.Nature reviews. Immunology · 2026Review
- Signal control during tissue regeneration in adult animals.Nature reviews. Molecular cell biology · 2026Review
- Tuning of G-CSFR signaling by de novo-designed agonists.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Causal effects of primary aldosteronism on inflammation and bone density: evidence from Mendelian randomization, animal, and clinical studies.Diabetology & metabolic syndrome · 2025Article
- Threonine phosphorylation of STAT1 safeguards gut epithelial integrity and restricts interferon-mediated cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Human IL-22 receptor-targeted small protein antagonist suppress murine DSS-induced colitis.Cell communication and signaling : CCS · 2024Article
- Endogenous IL-22 contributes to the pathogenesis of salivary gland dysfunction in the non-obese diabetic model of Sjögren's syndrome.Molecular immunology · 2024Article
- IL-22 in Atopic Dermatitis.Cells · 2024Review
- Strategies for targeting cytokines in inflammatory bowel disease.Nature reviews. Immunology · 2024Review
- Evaluating the inhibition of IL-17A and TNFα in a cartilage explant model cultured with Th17-derived cytokines.Journal of translational autoimmunity · 2024Article
- Structure-function of type I and III interferons.Current opinion in immunology · 2024Review
- Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition.Frontiers in immunology · 2024Article
- Distinct fibroblast functions associated with fibrotic and immune-mediated inflammatory diseases and their implications for therapeutic development.F1000Research · 2024Review
- LTβR-RelB signaling in intestinal epithelial cells protects from chemotherapy-induced mucosal damage.Frontiers in immunology · 2024Article
- IL-22 signaling promotes sorafenib resistance in hepatocellular carcinoma via STAT3/CD155 signaling axis.Frontiers in immunology · 2024Article
- Strategies to therapeutically modulate cytokine action.Nature reviews. Drug discovery · 2023Review
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Interleukin-22 (IL-22) acts on epithelial cells to promote tissue protection and regeneration, but can also elicit pro-inflammatory effects, contributing to disease pathology. Here, we engineered a high-affinity IL-22 super-agonist that enabled the structure determination of the IL-22-IL-22Rα-IL-10Rβ ternary complex to a resolution of 2.6 Å. Using structure-based design, we systematically destabilized the IL-22-IL-10Rβ binding interface to create partial agonist analogs that decoupled downstream STAT1 and STAT3 signaling. The extent of STAT bias elicited by a single ligand varied across tissues, ranging from full STAT3-biased agonism to STAT1/3 antagonism, correlating with IL-10Rβ expression levels. In vivo, this tissue-selective signaling drove tissue protection in the pancreas and gastrointestinal tract without inducing local or systemic inflammation, thereby uncoupling these opposing effects of IL-22 signaling. Our findings provide insight into the mechanisms underlying the cytokine pleiotropy and illustrate how differential receptor expression levels and STAT response thresholds can be synthetically exploited to endow pleiotropic cytokines with enhanced functional specificity.
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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.