Suppression of the Bacterial Antigen‐Specific T Cell Response and the Dendritic Cell Migration to the Lymph Nodes by Osteopontin

Begum, M. Dilara; Umemura, Masayuki; Kawa, Shigeyuki; Yahagi, Ayano; Hamada, Satoru; Oshiro, Kiyotetsu; Gotoh, Kazuyo; Nishizono, Akira; Uede, Toshimitsu; Matsuzaki, Goro

doi:10.1111/j.1348-0421.2007.tb03884.x

Cited by 19 publications

(18 citation statements)

References 49 publications

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“…In addition, Opn-deficient mice have a defect in trinitrochlorobenzeneinduced DC migration in draining LNs (37), whereas Opn treatment may dampen DC migration during bacterial infection (87). In the current study, WT colitic mice and Opn-deficient colitic recipients of transferred WT CD103 − DCs exhibited higher total MLN CD103 − DC numbers in comparison to Opn-deficient mice and recipients of Opn-deficient CD103 − DCs, respectively.…”

Section: Discussionmentioning

confidence: 66%

Osteopontin expression by CD103⁻dendritic cells drives intestinal inflammation

Kourepini

Aggelakopoulou

Alissafi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Intestinal CD103 − dendritic cells (DCs) are pathogenic for colitis. Unveiling molecular mechanisms that render these cells proinflammatory is important for the design of specific immunotherapies. In this report, we demonstrated that mesenteric lymph node CD103 − DCs express, among other proinflammatory cytokines, high levels of osteopontin (Opn) during experimental colitis. Opn expression by CD103 − DCs was crucial for their immune profile and pathogenicity, including induction of T helper (Th) 1 and Th17 cell responses. Adoptive transfer of Opn-deficient CD103 − DCs resulted in attenuated colitis in comparison to transfer of WT CD103 − DCs, whereas transgenic CD103 − DCs that overexpress Opn were highly pathogenic in vivo. Neutralization of secreted Opn expressed exclusively by CD103 − DCs restrained disease severity. Also, Opn deficiency resulted in milder disease, whereas systemic neutralization of secreted Opn was therapeutic. We determined a specific domain of the Opn protein responsible for its CD103 − DC-mediated proinflammatory effect. We demonstrated that disrupting the interaction of this Opn domain with integrin α9, overexpressed on colitic CD103 − DCs, suppressed the inflammatory potential of these cells in vitro and in vivo. These results add unique insight into the biology of CD103 − DCs and their function during inflammatory bowel disease.

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Section: Discussionmentioning

confidence: 66%

Osteopontin expression by CD103⁻dendritic cells drives intestinal inflammation

Kourepini

Aggelakopoulou

Alissafi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Similar efficacy of OPN antibody treatment was demonstrated in a study of experimental autoimmune encephalomyelitis, which correlated with reduced infiltration of inflammatory cells, most noticeably CD11bϩ macrophages, in spinal cord lesions (Zheng W, et al: unpublished observations). It is conceivable that OPN has a broad spectrum of proinflammatory properties that are all related to the key processes of the inflammatory cascade, including leukocyte migration and the induction of Th1 and Th17 cytokines (18,20,(37)(38)(39). Thus, selective blocking of these proinflammatory functions of OPN through selected motifs is likely to be therapeutically advantageous.…”

Section: Discussionmentioning

confidence: 99%

Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF‐κB and MAPK pathways in rheumatoid arthritis

Zheng¹,

R²,

Pan³

et al. 2009

Arthritis & Rheumatism

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Objective. Osteopontin (OPN) is a proinflammatory protein with a critical role in leukocyte migration. Although OPN has been implicated in rheumatoid arthritis (RA), its underlying mechanism remains unknown. In this study, we investigated the role and molecular mechanism of OPN in the induction of 2 key chemokines, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1␤ (MIP-1␤), in RA.Methods. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction were used to determine chemokine expression. Leukocyte migration in the presence of OPN was measured by chemotaxis assay. Signaling and molecular events were analyzed by immunoblotting and chromatin immunoprecipitation.Results. The effect of OPN on inflammatory cell migration was mediated through its unique property of inducing the expression of MCP-1 and MIP-1␤ in CD14؉ monocytes. The concentration of OPN was significantly elevated in RA patients and appeared to correlate with the serum levels of inflammation markers and increased expression of MCP-1 or MIP-1␤ in monocytes in RA patients. Endogenous production of OPN in RA synovial fluid was attributable to increased production of MCP-1 or MIP-1␤, and this effect could be blocked by an anti-OPN antibody. Furthermore, the structural motif responsible for this property resided within residues 50-83 of human OPN, sparing the known RGD or SVVYGLR sequences. It was evident that the effect of OPN on chemokine expression was mediated through both the NF-B and MAPK pathways, involving the activation of IKK␤, p38, and JNK.Conclusion. These results support a unique role of OPN in leukocyte migration, in the context of perpetuation of rheumatoid synovitis through the induction of MCP-1 and MIP-1␤.

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“…Elevation of OPN levels is believed to contribute to mononuclear cell infiltration and renal injury in murine anti-glomerular basement membrane nephritis; however it does not significantly contribute to the glomerular and tubulointerstitial mononuclear cell infiltration in an in vivo murine model of glomerulonephritis (Bonvini et al, 2000). OPN has been found to suppress bacterial antigen-specific T cell proliferation and DC migration when OPN is supplied together with heat-killed Listeria monocytogenes (Begum et al, 2007). In another study, when OPN -/-mice were analyzed after influenza infection in the lung, viral clearance, lung inflammation, and recruitment of effector T cells to the lung were comparable to OPN +/+ mice (Abel et al, 2005).…”

Section: Controversy About Opn's Effectsmentioning

confidence: 92%