title: IL-10 production by B cells is differentially regulated by immune-mediated and infectious stimuli and requires p38 activation.
abstract: IL-10 is an immune suppressive cytokine with pleiotropic effects on B cell biology. IL-10 production has a pivotal role for the regulatory suppressive functions that B cells exert in many physiological and pathological settings. Several exogenous stimuli and endogenous immune mediators can trigger IL-10-producing B cell maturation. To clarify and gain a better insight into the mechanisms of IL-10 production by B cells, we first compared the effects of LPS, CpG, agonistic CD40 mAb and BAFF on IL-10 production, and then we investigated the signal transduction mechanisms responsible for these responses. While infectious/danger stimuli determine the rapid production and release of IL-10 by B cells, a limited subset of CD40-poised, IL-10-competent B cells produce IL-10 in response to a later antigenic or infectious signal. Although BAFF is able to induce a similar subset of IL-10-competent B cells, these cells do not similarly respond to the same antigenic or infectious signals. Importantly, by using specific inhibitors of the MAP kinase pathways, we found that while il-10 gene expression triggered by the TLR agonists LPS and CpG is strongly dependent on p38 activity, the induction of IL-10 competence in CD40-activated B cells does not depend on ERK1/2, p38 or JNK pathways.
authors: Department of Medical and Biological Sciences, University of Udine, P.le M. Kolbe, 4, 33100 Udine, Italy.
authors: Francesca
authors: F
authors: Mion
authors: Department of Medical and Biological Sciences, University of Udine, P.le M. Kolbe, 4, 33100 Udine, Italy.
authors: Silvia
authors: S
authors: Tonon
authors: Department of Medical and Biological Sciences, University of Udine, P.le M. Kolbe, 4, 33100 Udine, Italy.
authors: Barbara
authors: B
authors: Toffoletto
authors: Department of Medical and Biological Sciences, University of Udine, P.le M. Kolbe, 4, 33100 Udine, Italy.
authors: Daniela
authors: D
authors: Cesselli
authors: Department of Medical and Biological Sciences, University of Udine, P.le M. Kolbe, 4, 33100 Udine, Italy. Electronic address: carlo.pucillo@uniud.it.
authors: Carlo E
authors: CE
authors: Pucillo
authors: Department of Medical and Biological Sciences, University of Udine, P.le M. Kolbe, 4, 33100 Udine, Italy.
authors: Gaetano
authors: G
authors: Vitale
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D007155:Immunologic Factors / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases
keywords: B cells; CD40; IL-10; MyD88; TLR; p38