Dataset Information

Integrin ?1 Promotes the Interaction of Murine IgG3 with Effector Cells.

ABSTRACT: Abs exert several of their effector functions by binding to cell surface receptors. For murine IgG3 (mIgG3), the identity of its receptors (and the very existence of a receptor) is still under debate, as not all mIgG3 functions can be explained by interaction with Fc?RI. This implies the existence of an alternate receptor, whose identity we sought to pinpoint. We found that blockage of integrin ?1 selectively hampered binding of mIgG3 to macrophages and mIgG3-mediated phagocytosis. Manganese, an integrin activator, increased mIgG3 binding to macrophages. Blockage of Fc?RI or Itgb1 inhibited binding of different mIgG3 Abs to variable extents. Our results are consistent with the notion that Itgb1 functions as part of an IgG receptor complex. Given the more ancient origin of integrins in comparison with Fc?R, this observation could have far-ranging implications for our understanding of the evolution of Ab-mediated immunity as well as in immunity to microorganisms, pathogenesis of autoimmune diseases, and Ab engineering.

SUBMITTER: Hawk CS

PROVIDER: S-EPMC6759214 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Integrin β1 Promotes the Interaction of Murine IgG3 with Effector Cells.

Hawk Carolyn Saylor CS Coelho Carolina C Oliveira Diane Sthefany Lima de DSL Paredes Verenice V Albuquerque Patrícia P Bocca Anamélia Lorenzetti AL Correa Dos Santos Ananésia A Rusakova Victoria V Holemon Heather H Silva-Pereira Ildinete I Felipe Maria Sueli Soares MSS Yagita Hideo H Nicola André Moraes AM Casadevall Arturo A

Journal of immunology (Baltimore, Md. : 1950) 20190320 9

Abs exert several of their effector functions by binding to cell surface receptors. For murine IgG3 (mIgG3), the identity of its receptors (and the very existence of a receptor) is still under debate, as not all mIgG3 functions can be explained by interaction with FcγRI. This implies the existence of an alternate receptor, whose identity we sought to pinpoint. We found that blockage of integrin β1 selectively hampered binding of mIgG3 to macrophages and mIgG3-mediated phagocytosis. Manganese, an ...[more]

PMID: 30894426

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Project description:ObjectiveTreg cells need to acquire an effector phenotype to function in settings of inflammation. Whether effector Treg cells can limit disease severity in lupus is unknown. Interferon regulatory factor 4 (IRF-4) is an essential controller of effector Treg cells and regulates their ability to express interleukin-10 (IL-10). In non-Treg cells, IRF-4 activity is modulated by interactions with DEF-6 and its homolog switch-associated protein 70 (SWAP-70). Although mice lacking both DEF-6 and SWAP-70 (double-knockout [DKO] mice) develop lupus, they display normal survival, suggesting that in DKO mice, Treg cells can moderate disease development. The purpose of this study was to investigate whether Treg cells from DKO mice have an increased capacity to become effector Treg cells due to the ability of DEF-6 and SWAP-70 to restrain IRF-4 activity.MethodsTreg cells were evaluated by fluorescence-activated cell sorting. The B lymphocyte-induced maturation protein 1 (BLIMP-1)/IL-10 axis was assessed by crossing DKO mice with BLIMP-1-YFP-10BiT dual-reporter mice. Deletion of IRF-4 in Treg cells from DKO mice was achieved by generating FoxP3(Cre) IRF-4(fl/fl) DKO mice.ResultsThe concomitant absence of DEF-6 and SWAP-70 led to increased numbers of Treg cells, which acquired an effector phenotype in a cell-intrinsic manner. In addition, Treg cells from DKO mice exhibited enhanced expression of the BLIMP-1/IL-10 axis. Notably, DKO effector Treg cells survived and expanded as disease progressed. The accumulation of Treg cells from DKO mice was associated with the up-regulation of genes controlling autophagy. IRF-4 was required for the expansion and function of effector Treg cells from DKO mice.ConclusionThis study revealed the existence of mechanisms that, by acting on IRF-4, can fine-tune the function and survival of effector Treg cells in lupus. These findings suggest that the existence of a powerful effector Treg cell compartment that successfully survives in an unfavorable inflammatory environment could limit disease development.

Dataset Information

Integrin ?1 Promotes the Interaction of Murine IgG3 with Effector Cells.

Publications

Integrin β1 Promotes the Interaction of Murine IgG3 with Effector Cells.

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