title: Co-activation through TLR4 and TLR9 but not TLR2 skews Treg-mediated modulation of Igs and induces IL-17 secretion in Treg: B cell co-cultures.
abstract: Whereas Th17 cells are associated with aggravated inflammation, regulatory T cells (Tregs) provide an environment to control overt responses. Nevertheless, Tregs display a certain degree of plasticity demonstrating that T cell differentiation processes are not absolute. Previously, we showed that human Treg clones induced B cells to produce IgG4. Here we focus on the actions of freshly isolated CD4(+)CD25(+)Foxp3(+)CD127(dim) Tregs on Ig production by B cells and the consequences of prior TLR activation of B cells. In the absence of TLR stimuli, Tregs, but not conventional T cells, dampened B cell proliferation, plasma cell formation and, with the exception of IgG4, all other Ig production. Although IgG4 levels were unchanged in total B cell:Treg co-cultures, levels were increased in Treg co-cultures of naive, but not memory, B cells. Triggering TLR on B cells skewed both Ig and cytokine secretion patterns and, surprisingly, Tregs within TLR4- and TLR9- but not TLR2-triggered B cell co-cultures up-regulated retinoic acid related orphan receptor (RORC) and produced IL-17. These data indicate that under conditions like bacterial or viral infections, B cells can escape Treg control, and provides an explanation as to why patients suffering from allergy or helminth infections display polar immunopathological symptoms despite being exposed to the same agent.
authors.affiliation: 1Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Clinic Bonn, Bonn, Germany.
authors.forename: Tomabu
authors.initials: T
authors.lastname: Adjobimey
authors.forename: Judith
authors.initials: J
authors.lastname: Satoguina
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.forename: Laura E
authors.initials: LE
authors.lastname: Layland
mesh_terms: D000917:Antibody Formation; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007156:Immunologic Memory; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000378:metabolism; D008213:Lymphocyte Activation; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007074:Immunoglobulin G; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9
keywords: B cells; IgG4; TLR; Th17; Treg; helminth; human