Galectin-9 Inhibits CD44–Hyaluronan Interaction and Suppresses a Murine Model of Allergic Asthma

Katoh, Shigeki; Ishii, Naoki; Nobumoto, Atsuya; Takeshita, Kenjiro; Dai, Shuyan; Shinonaga, Rika; Niki, Toshiro; Nishi, Nozomu; Tominaga, Akira; Yamauchi, Akira; Hirashima, Mitsuomi

doi:10.1164/rccm.200608-1243oc

Cited by 148 publications

(130 citation statements)

References 49 publications

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“…This model is supported by the finding that galectin-1 null mice and galectin-3 null mice have distinct types of T cell-mediated immune defects, indicating that these two galectins control T cell death at different points during T cell development and peripheral immune responses (49 -51). Similarly, administration of recombinant galectin-1, -3, or -9 has distinct therapeutic effects in mouse models of autoimmune disease such as asthma and nephritis (30,34,52).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, whereas Tim-3 may be required for galectin-9 death of Th1 cells, Tim-3 expression is not universally required for galectin-9 death of T cells. In addition, CD44 has been identi- fied as a T cell glycoprotein receptor for galectin-9 that is important for adhesion of T cells to hyaluronic acid (34). However, as Jurkat T cells do not express CD44 (Ref.…”

Section: Galectin-9-induced T Cell Death Requires Different Glycan LImentioning

confidence: 99%

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Structural Features of Galectin-9 and Galectin-1 That Determine Distinct T Cell Death Pathways

Earl

Jacobs

et al. 2008

Journal of Biological Chemistry

135

117

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The galectin family of lectins regulates multiple biologic functions, such as development, inflammation, immunity, and cancer. One common function of several galectins is the ability to trigger T cell death. However, differences among the death pathways triggered by various galectins with regard to glycoprotein receptors, intracellular death pathways, and target cell specificity are not well understood. Specifically, galectin-9 and galectin-1 both kill thymocytes, peripheral T cells, and T cell lines; however, we have found that galectin-9 and galectin-1 require different glycan ligands and glycoprotein receptors to trigger T cell death. The two galectins also utilize different intracellular death pathways, as galectin-9, but not galectin-1, T cell death was blocked by intracellular Bcl-2, whereas galectin-1, but not galectin-9, T cell death was blocked by intracellular galectin-3. Target cell susceptibility also differed between the two galectins, as galectin-9 and galectin-1 killed different subsets of murine thymocytes. To define structural features responsible for distinct activities of the tandem repeat galectin-9 and dimeric galectin-1, we created a series of bivalent constructs with galectin-9 and galectin-1 carbohydrate recognition domains connected by different peptide linkers. We found that the N-terminal carbohydrate recognition domain and linker peptide contributed to the potency of these constructs. However, we found that the C-terminal carbohydrate recognition domain was the primary determinant of receptor recognition, death pathway signaling, and target cell susceptibility. Thus, carbohydrate recognition domain specificity, presentation, and valency make distinct contributions to the specific effects of different galectins in initiating T cell death.Cell death is an essential factor in T cell development, which regulates selection of functional T cells during development in the thymus, as well as elimination of activated T cells after microbial infection or other exposure to antigen (1, 2). A number of distinct T cell death pathways have been described, including those triggered by members of the galectin family of vertebrate lectins (3-5). Galectin-1 was the first family member described to induce death of developing thymocytes and activated peripheral T cells, and the galectin-1 T cell death pathway is the best characterized to date. Specific glycoprotein receptors involved in galectin-1 death and specific types of O-and N-glycan ligands required for galectin-1 death have been identified, and galectin-1 has been shown to trigger a novel intracellular death pathway (6 -14). Other galectins have also been reported to trigger death of T cell lines and various T cell subsets, including galectin-2, galectin-3, galectin-8, and galectin-9 (15-19). Relatively little is known about the glycoprotein receptors, glycan ligands, and intracellular death pathways used by these galectins. However, our laboratory has found that galectin-1 and galectin-3 kill different subsets of thymocytes, and use distinct sets...

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Section: Discussionmentioning

confidence: 99%

Section: Galectin-9-induced T Cell Death Requires Different Glycan LImentioning

confidence: 99%

Structural Features of Galectin-9 and Galectin-1 That Determine Distinct T Cell Death Pathways

Earl

Jacobs

et al. 2008

Journal of Biological Chemistry

135

117

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“…Studies in models of inflammatory disease, such as complex immune-induced arthritis, allergic asthma and diabetes, support an anti-inflammatory role for gal-9 [10][11][12]. Unlike gal-1, gal-3 can both positively and negatively regulate the inflammatory response, depending on factors such as the specific inflammatory conditions or the type of target cell [13].…”

Section: Introductionmentioning

confidence: 99%

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

Fuente

Pérez‐Gala

Bonay

et al. 2012

The Journal of Pathology

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2 ABSTRACT.We have investigated the expression and role of galectin-1 and other galectins in psoriasis and in the Th1/Th17 effector and dendritic cell responses associated with this chronic inflammatory skin condition. To determine differences between psoriasis patients and healthy donors, galectins expression was analyzed by RT-PCR assays in skin samples and specifically on epidermal and peripheral blood dendritic cells by immunofluorescence and flow cytometry.In skin of healthy donors galectins 1, 3 and 9 were expressed in a high proportion of Langerhans cells. Also, galectins were differentially expressed in peripheral blood dendritic cell subsets; galectin-1 and galectin-9 were highly expressed in peripheral myeloid dendritic cells compared with plasmacytoid dendritic cells. We found that non-lesional as well as lesional skin samples from psoriasis patients had low levels of galectin-1 at mRNA and protein level in parallel with low levels of IL-10 mRNA compared with skin from healthy patients. However, only lesional skin samples expressed high levels of

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“…Galectin-9, in contrast, inhibits eosinophil recruitment and airways hyperreactivity when administered i.v. during antigen challenge, using the house dust mite model (16). Galectin-10 is expressed prominently in human (but not mouse) eosinophils (17), and was recently identified in CD25 + Tregs, where it serves to promote endogenous suppressor function (18).…”

mentioning

confidence: 99%

Eosinophils, galectins, and a reason to breathe

Rosenberg¹,

Druey²

2016

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

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Galectin-9 Inhibits CD44–Hyaluronan Interaction and Suppresses a Murine Model of Allergic Asthma

Abstract: We conclude that Gal-9 inhibits allergic inflammation of the airway and AHR by modulating CD44-dependent leukocyte recognition of the extracellular matrix.

Cited by 148 publications

References 49 publications

Structural Features of Galectin-9 and Galectin-1 That Determine Distinct T Cell Death Pathways

Structural Features of Galectin-9 and Galectin-1 That Determine Distinct T Cell Death Pathways

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

Eosinophils, galectins, and a reason to breathe

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