Galectin-9 Induces Maturation of Human Monocyte-Derived Dendritic Cells

Dai, Shuyan; Nakagawa, Ryusuke; Itoh, Akichika; Murakami, Hiromoto; Kashio, Yumiko; Abe, Hiroko; Katoh, Shigeki; Kontani, Keiichi; Kihara, Minoru; Zhang, Shulan; Hata, Toshiyuki; Nakamura, Takanori; Yamauchi, Akira; Hirashima, Mitsuomi

doi:10.4049/jimmunol.175.5.2974

Cited by 187 publications

(139 citation statements)

References 55 publications

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“…Thioredoxin is a ubiquitous intracellular enzyme with antioxidant activity 41 . Both galectins [42][43][44] and thioredoxin 45,46 have been shown to stimulate various leukocytes and endothelium ex vivo and when injected in vivo to stimulate inflammation. To what extent these molecules actually contribute to the deathinduced inflammatory response, if at all, is unknown.…”

Section: Intracellular Damps With Proinflammatory Activitymentioning

confidence: 99%

How dying cells alert the immune system to danger

2008

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When a cell dies in vivo the event does not go unnoticed. The host has evolved mechanisms to detect the death of cells and rapidly investigate the nature of their demise. If cell death is a result of natural causes, that is, it is part of normal physiological processes, then there is little threat to the organism. In this situation, little else is done other than removing the corpse. However, if cells have died as the consequence of some violence or disease, then both defence and repair mechanisms are mobilized. The importance of this process to host defence and disease pathogenesis has only been appreciated relatively recently. This article will review our current knowledge of these processes.The immune system was recognized in ancient times and rediscovered by Jenner and Pasteur based on its ability to confer protection upon repeat exposure to a pathogen. Through subsequent studies by Von Behring and others it rapidly became apparent that the immune system had the potential to respond not only to whole microorganisms, but to virtually any molecule that was "foreign" to the host. However, whereas injection of such molecules would often provoke a robust immune response, this did not invariably occur. Immunization protocols improved in the 1920s with the discovery by Ramon and Glenny of immunostimulatory molecules (adjuvants [G]) that could boost immune responses to co-administered antigens. Adjuvants were typically of microbial origin and became widely used to promote the effectiveness of immunizations. In the 1960s, Dresser showed that a foreign protein when highly purified would only elicit an immune response if it was admixed with a microbial adjuvant 1 . Injected by itself, the antigen not only failed to elicit immunity but actually induced a state of tolerance 2 . However, the significance of these observations was not well appreciated and adjuvants remained one of those things that everyone used because they were part of standard operating procedures.In 1989 Janeway put these empirical observations into a conceptual framework 3 (Fig. 1). He proposed that the immune system did not respond to all foreign antigens but only to those that are potentially associated with infection. The underlying idea here was that the immune system evolved to protect organisms against microorganisms and this discrimination between infectious versus noninfectious antigens focused defences on real threats rather than innocuous situations.At this time, it was already recognized that in order to stimulate T cell responses, antigens had to first be acquired and presented on MHC molecules of an antigen presenting cell (APC). Moreover, it was further known that APCs also provided additional costimulatory signals necessary to activate T cells. Janeway incorporated these principles into his model (Fig. 1). He postulated that the discrimination between infectious and noninfectious non-self molecules was made by the APCs of the innate immune system through receptors that would recognize pathogen-associated molecular patterns (PAMP...

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Section: Intracellular Damps With Proinflammatory Activitymentioning

confidence: 99%

How dying cells alert the immune system to danger

2008

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“…Because of the diverse roles played by galectins in regulating key aspects of the innate immune system of vertebrates (Vasta et al, 2004a;Rabinovitch et al, 2002), such as phagocytosis (Sano et al, 2003), pattern-recognition of parasite antigens (Young and Meeusen, 2004;Van der Berg et al, 2004), and especially regulation of T-cell activation and apoptosis by gal-4 and gal-9 (Ilarregui et al, 2005;Dai et al, 2005), the finding of BgGal expression in circulating phagocytic cells of B. glabrata was of particular interest. Hemocytes are the primary line of immune defense against invading microbial and parasitic infections in molluscs and, upon pathogen recognition, are capable of eliminating infections through phagocytic or encapsulation responses (Bayne et al, 2001;Labrenche et al, 2006).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Molecular and functional characterization of a tandem-repeat galectin from the freshwater snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni

Yoshino

Dinguirard

Kunert

et al. 2008

Gene

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In the present study, a tandem-repeat type galectin was characterized from an embryonic cell line (Bge) and circulating hemocytes of the snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni. The predicted B. glabrata galectin (BgGal) protein of 32 kDa possessed 2 carbohydrate recognition domains, each displaying 6 of 8 conserved amino acids involved in galactoside-binding activity. A recombinant BgGal (rBgGal) demonstrated hemagglutinating activity against rabbit erythrocytes, which was specifically inhibited by galactosecontaining sugars (lacNAc/lac > galNAc/gal). Although native galectin was immunolocalized in the cytoplasm of Bge cells and the plasma membrane of a subset of snail hemocytes (60%), it was not detected in cell-free plasma by Western blot analysis. The findings that rBgGal selectively recognizes the schistosome-related sugar, lacNAc, and strongly binds to hemocytes and the tegument of S. mansoni sporocysts in a sugar-inhibitable fashion suggest that hemocyte-bound galectin may be serving as pattern recognition receptor for this, or other pathogens possessing appropriate sugar ligands. Based on molecular and functional features, BgGal represents an authentic galectin, the first to be fully characterized in the medically-important molluscan Class Gastropoda.

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“…5A shows that the presence of tg gal-1 increased the capacity of gal-1-DC to present the IE␣ [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] peptide to naive 1H3.1 T cells significantly compared with controls. The phenomenon was Ag-specific because gal-1-DC did not induce proliferation of 1H3.1 cells in the absence of IE␣ [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] (Fig. 5A).…”

Section: Expression Of Tg Gal-1 Enhances the Stimulatory Ability Of DCmentioning

confidence: 99%

“…For Ag presentation assays, FACS-sorted (CD11c ϩ ) untreated and RAdtransduced B10 DC (DC purity Ն93%) were gamma irradiated (20 Gy), pulsed with the BALB/c peptide IE␣ [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] (1 g/ml), and used as stimulators of 10 5 naive CD4 ϩ 1H3. …”

Section: Assay Of Ag Presentation Mlr and Elisamentioning

confidence: 99%

Transgenic Galectin-1 Induces Maturation of Dendritic Cells That Elicit Contrasting Responses in Naive and Activated T Cells

Perone¹,

Larregina²,

Shufesky³

et al. 2006

The Journal of Immunology

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Dendritic cells (DC) are professional APC that control the balance between T cell immunity and tolerance. Genetic engineering of DC to regulate the outcome of the immune response is an area of intense research. Galectin (gal)-1 is an endogenous lectin that binds to glycoproteins and exerts potent regulatory effects on T cells. Consequently, gal-1 participates in central deletion of thymocytes and exerts therapeutic effects on experimental models of T cell-mediated autoimmune disorders and graft-vs-host disease. Together, these observations strongly indicate that engineering DC to express transgenic (tg) gal-1 may be beneficial to treat T cell-mediated disorders. In this study, we have investigated the impact of the expression of high levels of tg gal-1 on maturation/activation of DC and on their T cell stimulatory function. Murine DC were transduced with a recombinant adenovirus encoding hu gal-1 (gal-1-DC). Tg gal-1 was exported by a nonclassical pathway through exosomes and was retained on the DC surface inducing segregation of its ligand CD43. Expression of tg gal-1 triggered activation of DC determined by induction of a more mature phenotype, increased levels of mRNA for proinflammatory cytokines, and enhanced ability to stimulate naive T cells. Conversely, gal-1-DC induced rapid apoptosis of activated T cells. In vivo, gal-1-DC increased significantly the sensitization phase of contact hypersensitivity assays while inducing a drastic inhibition of the elicitation phase by triggering apoptosis of activated T cells in the dermis. Gal-1-DC represent a novel tool to control differentially the afferent and efferent arms of the T cell response.

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Galectin-9 Induces Maturation of Human Monocyte-Derived Dendritic Cells

Cited by 187 publications

References 55 publications

How dying cells alert the immune system to danger

How dying cells alert the immune system to danger

Molecular and functional characterization of a tandem-repeat galectin from the freshwater snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni

Transgenic Galectin-1 Induces Maturation of Dendritic Cells That Elicit Contrasting Responses in Naive and Activated T Cells

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