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Review
. 2016:2016:7675437.
doi: 10.1155/2016/7675437. Epub 2016 Dec 20.

Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases

Nausicaa Clemente  1 , Davide Raineri  1 , Giuseppe Cappellano  2 , Elena Boggio  1 , Francesco Favero  1 , Maria Felicia Soluri  1 , Chiara Dianzani  3 , Cristoforo Comi  4 , Umberto Dianzani  1 , Annalisa Chiocchetti  1
Affiliations
Review

Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases

Nausicaa Clemente et al. J Immunol Res. 2016.

Abstract

Osteopontin (OPN) regulates the immune response at multiple levels. Physiologically, it regulates the host response to infections by driving T helper (Th) polarization and acting on both innate and adaptive immunity; pathologically, it contributes to the development of immune-mediated and inflammatory diseases. In some cases, the mechanisms of these effects have been described, but many aspects of the OPN function remain elusive. This is in part ascribable to the fact that OPN is a complex molecule with several posttranslational modifications and it may act as either an immobilized protein of the extracellular matrix or a soluble cytokine or an intracytoplasmic molecule by binding to a wide variety of molecules including crystals of calcium phosphate, several cell surface receptors, and intracytoplasmic molecules. This review describes the OPN structure, isoforms, and functions and its role in regulating the crosstalk between innate and adaptive immunity in autoimmune diseases.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Genomic, transcriptional, and protein features of OPN. The figure shows in the upper panel the genomic organization of the SPP1 gene and the relevant single nucleotide polymorphisms. OPN is transcribed with 3 splicing variants: variant a contains exons 2–7 while variants b and c lack exons 5 and 4, respectively (middle panel). OPN transcripts have also two starting points generating a secreted or/and intracellular form. Several posttranslational modifications are also shown (lower panel) including phosphorylation (asterisks), glycosylation, and sulfation sites. Proteases (thrombin and matrix metalloproteinase, MMP) cleavage sites are also depicted.
Figure 2
Figure 2
OPN mediates innate-adaptive immune crosstalk. Soluble OPN (OPN) acts on macrophages upregulating interleukin- (IL-) 12 production and mediates T helper (Th) 1 development. It also acts on Th cells, inducing the production of IL-17 and inhibiting secretion of IL-10 resulting in Th17 polarization. In conventional dendritic cell (cDC), iOPN inhibits IL-27 expression and enhances the response of Th17 cells. In plasmacytoid DC (pDC), it enhances interferon (IFN) α expression. iOPN has also a key role in T follicular helper (TFH) cells, since during activation iOPN translocate into the nucleus and sustains TFH polarization. Big and empty arrows show OPN production; thin arrows indicate OPN actions.
See this image and copyright information in PMC

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