title: Membrane-bound IL-22 after de novo production in tuberculosis and anti-Mycobacterium tuberculosis effector function of IL-22+ CD4+ T cells.
abstract: The role of IL-22-producing CD4(+) T cells in intracellular pathogen infections is poorly characterized. IL-22-producing CD4(+) T cells may express some effector molecules on the membrane, and therefore synergize or contribute to antimicrobial effector function. This hypothesis cannot be tested by conventional approaches manipulating a single IL-22 cytokine at genetic and protein levels, and IL-22(+) T cells cannot be purified for evaluation due to secretion nature of cytokines. In this study, we surprisingly found that upon activation, CD4(+) T cells in Mycobacterium tuberculosis-infected macaques or humans could evolve into T effector cells bearing membrane-bound IL-22 after de novo IL-22 production. Membrane-bound IL-22(+) CD4(+) T effector cells appeared to mature in vivo and sustain membrane distribution in highly inflammatory environments during active M. tuberculosis infection. Near-field scanning optical microscopy/quantum dot-based nanoscale molecular imaging revealed that membrane-bound IL-22, like CD3, distributed in membrane and engaged as ∼100-200 nm nanoclusters or ∼300-600 nm nanodomains for potential interaction with IL-22R. Importantly, purified membrane-bound IL-22(+) CD4(+) T cells inhibited intracellular M. tuberculosis replication in macrophages. Our findings suggest that IL-22-producing T cells can evolve to retain IL-22 on membrane for prolonged IL-22 t(1/2) and to exert efficient cell-cell interaction for anti-M. tuberculosis effector function.
authors.affiliation: Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Gucheng
authors.initials: G
authors.lastname: Zeng
authors.forename: Crystal Y
authors.initials: CY
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Shuyu
authors.initials: S
authors.lastname: Yao
authors.forename: Richard C
authors.initials: RC
authors.lastname: Wang
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D000097043:Interleukin-22
chemical_list: D000900:Anti-Bacterial Agents; D018836:Inflammation Mediators; D007378:Interleukins; D008565:Membrane Proteins; D000097043:Interleukin-22