CD11b regulates the Treg/Th17 balance in murine arthritis via IL‐6

Stevanin, Mathias; Busso, Nathalie; Chobaz, Véronique; Pigni, Matteo; Ghassem-Zadeh, Sahar; Zhang, Li; Acha‐Orbea, Hans; Ehirchiou, Driss

doi:10.1002/eji.201646565

Cited by 33 publications

(29 citation statements)

References 39 publications

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“…This cell line has already proven to be a reliable model for the study of cDC2s. Indeed, in a recent report from our group, resistance to collagen induced arthritis (CIA) was partially recovered by the adoptive transfer of CD4 − MutuDC2s in a CIA-susceptible CD11b −/− mouse model, highlighting a potential tolerogenic role of cDC2s in the modulation of autoimmune responses (99). Furthermore, the CD4 − MutuDC2s have been successfully transduced with a CRISPR-Cas9 editing system to generate a new CD11b −/− CD4 − MutuDC2 line (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of a Functionally Competent Type 2 Conventional Dendritic Cell Line

et al. 2018

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Dendritic cells (DCs) are the most potent antigen presenting cells and possess an incomparable ability to activate and instruct T cells, which makes them one of the cornerstones in the regulation of the cross-talk between innate and adaptive immunity. Therefore, a deep understanding of DC biology lays the foundations to describe and to harness the mechanisms that regulate the development of the adaptive response, with clear implications in a vast array of fields such as the study of autoimmune diseases and the development of new vaccines. However, the great difficulty to obtain large quantities of viable non-activated DCs for experimentation have considerably hindered the progress of DC research. Several strategies have been proposed to overcome these limitations by promoting an increase of DC abundance in vivo, by inducing DC development from DC progenitors in vitro and by generating stable DC lines. In the past years, we have described a method to derive immortalized stable DC lines, named MutuDCs, from the spleens of Mushi1 mice, a transgenic mouse strain that express the simian virus 40 Large T-oncogene in the DCs. The comparison of these DC lines with the vast variety of DC subsets described in vivo has shown that all the MutuDC lines that we have generated so far have phenotypic and functional features of type 1 conventional DCs (cDC1s). With the purpose of deriving DC lines with characteristics of type 2 conventional DCs (cDC2s), we bred a new Batf3−/− Mushi1 murine line in which the development of the cDC1 subset is severely defective. The new MutuDC line that we generated from Batf3−/− Mushi1 mice was phenotypically and functionally characterized in this work. Our results demonstrated that all the tested characteristics of this new cell line, including the expression of subset-determining transcription factors, the profile of cytokine production and the ability to present antigens, are comparable with the features of splenic CD4− cDC2s. Therefore, we concluded that our new cell line, that we named CD4− MutuDC2 line, represents a valuable model for the CD4− cDC2 subset.

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Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of a Functionally Competent Type 2 Conventional Dendritic Cell Line

et al. 2018

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“…As outlined above, LFA-1 is required for the differentiation and suppressive activity of Treg, and its deficiency actually promoted induction of proinflammatory Th17 cells [71,72]. Furthermore, MAC-1 was shown to be required for the induction of peripheral tolerance by suppressing IL-6 secretion and subsequent Th17 differentiation in a model of orally induced tolerance in mouse [255]. Furthermore, MAC-1 maintained autoreactive B cell tolerance by inhibiting B cell receptor signaling [127].…”

Section: Functions Of β2 Integrins In Autoimmunitymentioning

confidence: 92%

“…In a murine collagen-induced arthritis (CIA) model, MAC-1 expression prevented early disease onset, and decreased the severity of CIA via controlling IL-6 secretion and subsequent Th17 polarization of lymphocytes [255]. On C57BL6 genetic background, CD11b −/− mice developed CIA of high severity and incidence, whereas WT mice were fully protected from the disease.…”

Section: Mac-1mentioning

confidence: 99%

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

Bednarczyk

Stege

Grabbe

et al. 2020

IJMS

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β2 integrins are heterodimeric surface receptors composed of a variable α (CD11a-CD11d) and a constant β (CD18) subunit and are specifically expressed by leukocytes. The α subunit defines the individual functional properties of the corresponding β2 integrin, but all β2 integrins show functional overlap. They mediate adhesion to other cells and to components of the extracellular matrix (ECM), orchestrate uptake of extracellular material like complement-opsonized pathogens, control cytoskeletal organization, and modulate cell signaling. This review aims to delineate the tremendous role of β2 integrins for immune functions as exemplified by the phenotype of LAD-I (leukocyte adhesion deficiency 1) patients that suffer from strong recurrent infections. These immune defects have been largely attributed to impaired migratory and phagocytic properties of polymorphonuclear granulocytes. The molecular base for this inherited disease is a functional impairment of β2 integrins due to mutations within the CD18 gene. LAD-I patients are also predisposed for autoimmune diseases. In agreement, polymorphisms within the CD11b gene have been associated with autoimmunity. Consequently, β2 integrins have received growing interest as targets in the treatment of autoimmune diseases. Moreover, β2 integrin activity on leukocytes has been implicated in tumor development.

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“…Accordingly, in this issue, Stevanin et al. observed that in the course of collagen‐induced arthritis, CD11b −/− mice exhibited much higher IL‐6 levels as compared with those of WT control animals. The IL‐6 was produced by DCs and peritoneal macrophages.…”

mentioning

confidence: 98%

“…The report of Stevanin et al. has set the stage for further investigation not only of the biologic role of CD11b (why does CD11b not interfere with murine collagen‐induced arthritis in mice with H‐2 q or H‐2 r MHC haplotypes?) but also of the decisive role of the cytokine IL‐6 in the development of RA and other autoimmune diseases.…”

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confidence: 99%