IL-13 effector functions.
IL-13 was first recognized for its effects on B cells and monocytes, where it upregulated class II expression, promoted IgE class switching and inhibited inflammatory cytokine production. It was also thought to be functionally redundant with IL-4. However, studies conducted with knockout mice, neutralizing antibodies, and novel antagonists demonstrate that IL-13 possesses several unique effector functions that distinguish it from IL-4. Resistance to most gastrointestinal nematodes is mediated by type-2 cytokine responses, in which IL-13 plays a dominant role. By regulating cell-mediated immunity, IL-13 modulates resistance to intracellular organisms including Leishmania major, Leishmania mexicana, and Listeria monocytogenes. In the lung, IL-13 is the central mediator of allergic asthma, where it regulates eosinophilic inflammation, mucus secretion, and airway hyperresponsiveness. Manipulation of IL-13 effector function may also prove useful in the treatment of some cancers like B-cell chronic lymphocytic leukemia and Hodgkin's disease, where IL-13 modulates apoptosis or tumor cell growth. IL-13 can also inhibit tumor immunosurveillance. As such, inhibitors of IL-13 might be effective as cancer immunotherapeutics by boosting type-1-associated anti-tumor defenses. Finally, IL-13 was revealed as a potent mediator of tissue fibrosis in both schistosomiasis and asthma, which indicates that it is a key regulator of the extracellular matrix. The mechanisms that regulate IL-13 production and/or function have also been investigated, and IL-4, IL-12, IL-18, IFN-gamma, IL-10, TGF-beta, TNF-alpha, and the IL-4/IL-13 receptor complex play important roles. This review highlights the effector functions of IL-13 and describes multiple pathways for modulating its activity in vivo.
Wynn
Thomas A
TA
Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. twynn@niaid.nih.gov
D000818:Animals; D001249:Asthma / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005355:Fibrosis; D005767:Gastrointestinal Diseases / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology*; D008174:Lung Diseases, Parasitic / Q000276:immunology; D051379:Mice; D009349:Nematode Infections / Q000276:immunology; D009369:Neoplasms / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology
D016207:Cytokines; D018793:Interleukin-13