Hyaluronan binding identifies the most proliferative activated and memory T cells

Maeshima, Nina; Poon, Grace F. T.; Dosanjh, Manisha; Felberg, Jackie; Lee, Sally S.M.; Cross, Jennifer; Birkenhead, Darlene; Johnson, Pauline

doi:10.1002/eji.201040870

Cited by 21 publications

(47 citation statements)

References 33 publications

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“…In addition, chondroitinase ABC did not affect hyaluronan binding in unstimulated macrophages, suggesting that either the enzyme could not access the site on CD44 on the macrophage surface or that the six-sugar stub left after chondroitinase digestion is sufficient to mediate its negative effect. It is also possible that regulation by chondroitin sulfate may operate in other immune cells as the expression of the human CD44s mutant, S180A, which lacks the site of chondroitin sulfate addition, led to constitutive hyaluronan binding in Jurkat T cells (56), raising the possibility that T cells, which up-regulate hyaluronan binding upon antigen recognition (21,22), may also regulate hyaluronan binding by regulating chondroitin sulfate addition to CD44.…”

Section: Discussionmentioning

confidence: 99%

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Differential Use of Chondroitin Sulfate to Regulate Hyaluronan Binding by Receptor CD44 in Inflammatory and Interleukin 4-activated Macrophages

Ruffell¹,

Poon

Lee³

et al. 2011

Journal of Biological Chemistry

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CD44 is a cell surface receptor for the extracellular matrix glycosaminoglycan hyaluronan and is involved in processes ranging from leukocyte recruitment to wound healing. In the immune system, the binding of hyaluronan to CD44 is tightly regulated, and exposure of human peripheral blood monocytes to inflammatory stimuli increases CD44 expression and induces hyaluronan binding. Here we sought to understand how mouse macrophages regulate hyaluronan binding upon inflammatory and anti-inflammatory stimuli. Mouse bone marrow-derived macrophages stimulated with tumor necrosis factor ␣ or lipopolysaccharide and interferon-␥ (LPS/IFN␥) induced hyaluronan binding by up-regulating CD44 and down-regulating chondroitin sulfation on CD44. Hyaluronan binding was induced to a lesser extent in interleukin-4 (IL-4)-activated macrophages despite increased CD44 expression, and this was attributable to increased chondroitin sulfation on CD44, as treatment with ␤-D-xyloside to prevent chondroitin sulfate addition significantly enhanced hyaluronan binding. These changes in the chondroitin sulfation of CD44 were associated with changes in mRNA expression of two chondroitin sulfotransferases, CHST3 and CHST7, which were decreased in LPS/IFN␥-stimulated macrophages and increased in IL-4-stimulated macrophages. Thus, inflammatory and anti-inflammatory stimuli differentially regulate the chondroitin sulfation of CD44, which is a dynamic physiological regulator of hyaluronan binding by CD44 in mouse macrophages.Macrophages differentiate from peripheral blood monocytes upon recruitment to the tissues. Under homeostatic conditions this process occurs constitutively to maintain a population of resident macrophages that provide a first line of defense against invading microorganisms (for review, see Refs. 1 and 2). This is of particular importance in some tissues, such as the lungs, where phagocytosis of bacteria by resident alveolar macrophages can be sufficient to clear infection (3). During inflammatory conditions, recruitment of a different subpopulation of monocytes occurs, and the number of macrophages in the tissues is greatly increased. Macrophages initially undergo "classical activation" in response to IFN␥ and toll-like receptor (TLR) 6 ligands such as LPS and display increased anti-microbial abilities due to increased production of reactive nitrogen and oxygen species (for review, see Refs. 4 and 5). The production of proinflammatory and T helper cell 1 (T H 1)-polarizing cytokines by these LPS-and IFN␥-polarized (M1) macrophages affects both the local and systemic immune response. Recruited macrophages are also important for resolving inflammation, as they phagocytose inflammation-inducing agents such as bacteria, cellular debris, and degraded extracellular matrix components (6, 7). Furthermore, increased levels of anti-inflammatory or T helper cell 2 (T H 2)-polarizing cytokines such as IL-4 result in the "alternative activation" of macrophages. These alternatively activated (M2) macrophages produce anti-inflammatory cytokines ...

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Section: Discussionmentioning

confidence: 99%

“…20). T lymphocytes are induced to bind hyaluronan after activation with antigen (21,22), whereas proinflammatory cytokines, such as TNF␣, induce hyaluronan binding in human peripheral blood monocytes (23,24) and endothelial cells (25). M2-inducing cytokines such as IL-4, meanwhile, can inhibit hyaluronan binding in human peripheral blood monocytes (23).…”

mentioning

confidence: 99%

Differential Use of Chondroitin Sulfate to Regulate Hyaluronan Binding by Receptor CD44 in Inflammatory and Interleukin 4-activated Macrophages

Ruffell¹,

Poon

Lee³

et al. 2011

Journal of Biological Chemistry

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“…Considering the ubiquitous distribution of CD44 and HA, tight regulation of the HA-binding ability of CD44 is likely to play a critical role in immunological responses. In fact, CD44 on resting T cells does not bind HA, but can be induced to bind it upon T cell activation with antigen via the T cell receptor (TCR) (DeGrendele et al, 1997;Lesley et al, 1994;Ariel et al, 2000;Firan et al, 2006;Maeshima et al, 2011). Studies report that various posttranslational modifications on CD44, including glycosylation (Katoh et al, 1995;English et al, 1998;Skelton et al, 1998), chondroitin sulfate addition (Levesque and Haynes, 1999;Ruffell et al, 2011), and sulfation (Maiti et al, 1998;Brown et al, 2001), affect its HA-binding ability.…”

Section: Introductionmentioning

confidence: 99%

Membrane cholesterol modulates the hyaluronan-binding ability of CD44 in T lymphocytes and controls rolling under shear flow

Murai

Sato

et al. 2013

Journal of Cell Science

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SummaryThe adhesion of circulating lymphocytes to the surface of vascular endothelial cells is important for their recruitment from blood to secondary lymphoid organs and to inflammatory sites. CD44 is a key adhesion molecule for this interaction and its ligand-binding ability is tightly regulated. Here we show that the hyaluronan-binding ability of CD44 in T cells is upregulated by the depletion of membrane cholesterol with methyl-b-cyclodextrin (MbCD), which disintegrates lipid rafts, i.e. cholesterol-and sphingolipid-enriched membrane microdomains. Increasing concentrations of MbCD led to a dose-dependent decrease in cellular cholesterol content and to upregulation of hyaluronan binding. Additionally, a cholesterol-binding agent filipin also increased hyaluronan binding. Cholesterol depletion caused CD44 to be dispersed from cholesterol-enriched membrane microdomains. Cholesterol depletion also increased the number of cells undergoing rolling adhesion under physiological flow conditions. Our results suggest that the ligand-binding ability of CD44 is governed by its cholesterol-dependent allocation to membrane microdomains at the cell surface. These findings provide novel insight into the regulation of T cell adhesion under blood flow.

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“…Several studies suggest that hyaluronan may have proinflammatory roles in the context of CNS autoimmunity: 1) it accumulates in demyelinated CNS lesions in MS and EAE (5,6); 2) HA production by dendritic cells and T-cells promotes antigen presentation and enhances T-cell activation and proliferation (2,3,7,8); 3) HA-CD44 interactions at the CNS vascular endothelium facilitate lymphocyte binding to vessels and CNS infiltration (9 -11); and 4) hyaluronan fragments signal through both Toll-like receptors (TLR) 2 and 4 and thereby stimulate inflammatory gene expression in immune cells (12).…”

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confidence: 99%

Inhibition of Hyaluronan Synthesis Protects against Central Nervous System (CNS) Autoimmunity and Increases CXCL12 Expression in the Inflamed CNS

Mueller

Yoon

Sadiq

2014

Journal of Biological Chemistry

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Background: Hyaluronan accumulates in chronic demyelinated multiple sclerosis (MS) lesions. Results: 4-Methylumbelliferone (4MU) inhibits HA synthesis, is protective in active and passive MS models, modulates T-cell responses, and prevents CXCL12 suppression within inflamed and non-inflamed CNS tissue. Conclusion: Inhibition of hyaluronan synthesis protects against CNS inflammation. Significance: Study data substantiate a link between hyaluronan and CNS inflammation.

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Hyaluronan binding identifies the most proliferative activated and memory T cells

Cited by 21 publications

References 33 publications

Differential Use of Chondroitin Sulfate to Regulate Hyaluronan Binding by Receptor CD44 in Inflammatory and Interleukin 4-activated Macrophages

Differential Use of Chondroitin Sulfate to Regulate Hyaluronan Binding by Receptor CD44 in Inflammatory and Interleukin 4-activated Macrophages

Membrane cholesterol modulates the hyaluronan-binding ability of CD44 in T lymphocytes and controls rolling under shear flow

Inhibition of Hyaluronan Synthesis Protects against Central Nervous System (CNS) Autoimmunity and Increases CXCL12 Expression in the Inflamed CNS

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