Academic Journal
Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.
| Τίτλος: | Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications. |
|---|---|
| Συγγραφείς: | Upadhyay S; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA., Nagampalli R; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA., Resende S; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA., Kanneganti TD; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA. Thirumala-Devi.Kanneganti@StJude.org. |
| Πηγή: | Cell research [Cell Res] 2026 Oct; Vol. 36 (10), pp. 747-768. Date of Electronic Publication: 2026 Sep 04. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9425763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1748-7838 (Electronic) Linking ISSN: 10010602 NLM ISO Abbreviation: Cell Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: Basingstoke, England : Nature Publishing Group Original Publication: Beijing, China : Science Press, 1990- |
| Ιατρικοί όροι (MeSH): | Inflammasomes*/immunology , Inflammasomes*/metabolism , Inflammasomes*/chemistry , Immunity, Innate*, Inflammation/immunology ; Humans ; Animals ; Innate Immunity Recognition ; Signal Transduction |
| Περίληψη: | Innate immunity provides a critical first line of defense against pathogens and homeostatic perturbations. Pattern recognition receptors detect these disruptions and initiate immune responses through multi-protein complex formation to drive inflammatory signaling and cell death pathways. Key cytosolic complexes formed by these sensors include inflammasomes and PANoptosomes. Inflammasomes induce caspase-1 activation and the subsequent maturation of interleukin (IL)-1β and IL-18, and they can act as integral components of larger PANoptosomes, whose formation and functions have been defined by genetic, biochemical, and single-cell imaging evidence. PANoptosomes induce lytic, inflammatory cell death (PANoptosis) and promote the release of damage-associated molecular patterns (DAMPs) and cytokines beyond IL-1β and IL-18, including TNF, IFNs, IL-6, and others. Given their critical functions in driving cell death and the release of cytokines and DAMPs, dysregulation of innate immune sensors is associated with a wide range of diseases, including infections, autoinflammatory syndromes, cardiovascular disorders, neurodegeneration, metabolic conditions, and cancer. Therefore, understanding innate immune sensors and how they assemble inflammasomes and PANoptosomes to drive cell death is critical for identifying therapeutic strategies. In this review, we discuss innate immune sensors that form inflammasomes and PANoptosomes, such as NLRP1, NLRP3, NLRC4, AIM2, Pyrin, and others. We highlight recent structural and mechanistic insights into these sensors, along with emerging structural studies of inflammasome assemblies and the biochemical and functional evidence supporting the formation of PANoptosomes. Given the physiological relevance of innate immune sensors and the complexes they form across the disease spectrum, an improved understanding of their structure-function relationships will be critical for informing therapeutic strategies that target these molecules, their associated complexes, and their physiological functions. (© 2026. The Author(s).) |
| Competing Interests: | Competing interests: The authors declare no competing interests. |
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| Grant Information: | AI101935 U.S. Department of Health & Human Services | National Institutes of Health (NIH); AI124346 U.S. Department of Health & Human Services | National Institutes of Health (NIH); AI160179 U.S. Department of Health & Human Services | National Institutes of Health (NIH); AR056296 U.S. Department of Health & Human Services | National Institutes of Health (NIH); CA253095 U.S. Department of Health & Human Services | National Institutes of Health (NIH); N/A American Lebanese Syrian Associated Charities (ALSAC) |
| Substance Nomenclature: | 0 (Inflammasomes) |
| Entry Date(s): | Date Created: 20260904 Date Completed: 20261007 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| DOI: | 10.1038/s41422-026-01287-9 |
| PMID: | 42693250 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1748-7838 |
|---|---|
| DOI: | 10.1038/s41422-026-01287-9 |