Functional Role Played by the Glycosylphosphatidylinositol Anchor Glycan of CD48 in Interleukin-18-induced Interferon-γ Production

Fukushima, Keiko; Ikehara, Yukio; Yamashita, Katsuko

doi:10.1074/jbc.m413297200

Cited by 25 publications

(22 citation statements)

References 31 publications

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“…A recent report has also described a complex formation among the IL-18R␣, IL-18, and CD48 that in turn binds the IL-18R␤. This complex has been implicated in delivering the IL-18 signal (53). If the latter finding has any relation to the present discussion on 2B4-mediated interactions with CD48 remains to be investigated.…”

Section: T Cells Costimulate Each Other Through 2b4-cd48 Interactionsmentioning

confidence: 64%

2B4/CD48-Mediated Regulation of Lymphocyte Activation and Function

Assarsson

Kambayashi

Persson

et al. 2005

The Journal of Immunology

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2B4 (CD244) is a member of the CD2 subset of the Ig superfamily. This molecule is expressed on innate immune cells, including NK cells, and on subsets of T cells. The 2B4 molecule interacts with CD48, which is widely expressed on hemopoietic cells. Although earlier reports demonstrated a role for 2B4 as an activating receptor in both mice and humans, recent studies of 2B4-deficient mice have suggested that 2B4 functions predominantly as an inhibitory receptor in mice. In addition, 2B4 may also act as a costimulatory ligand for cells expressing CD48. Thus, the 2B4 molecule is more multifunctional than previously understood. In this study, we delineate the current view of 2B4-CD48 interactions among lymphocytes and other cells.

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Section: T Cells Costimulate Each Other Through 2b4-cd48 Interactionsmentioning

confidence: 64%

2B4/CD48-Mediated Regulation of Lymphocyte Activation and Function

Assarsson

Kambayashi

Persson

et al. 2005

The Journal of Immunology

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“…In addition, transgenic overexpression of pro-IL-18 by keratinocytes induces the development of atopic dermatitis (41,42). Intriguingly, IL-18 interacts with CD48 to induce its signaling cascades (43). Thus, IL-18 stimulation of CD48 may promote allergic responses.…”

Section: Discussionmentioning

confidence: 99%

CD48 Is Critically Involved in Allergic Eosinophilic Airway Inflammation

Munitz

Bachelet²,

Finkelman³

et al. 2007

Am J Respir Crit Care Med

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Rationale: Despite ongoing research, the molecular mechanisms controlling asthma are still elusive. CD48 is a glycosylphosphatidylinositolanchored protein involved in lymphocyte adhesion, activation, and costimulation. Although CD48 is widely expressed on hematopoietic cells and commonly studied in the context of natural killer and cytotoxic T cell functions, its role in helper T cell type 2 settings has not been examined. Objectives: To evaluate the expression and function of CD48, CD2, and 2B4 in a murine model of allergic eosinophilic airway inflammation. Methods: Allergic eosinophilic airway inflammation was induced by ovalbumin (OVA)-alum sensitization and intranasal inoculation of OVA or, alternatively, by repeated intranasal inoculation of Aspergillus fumigatus antigen in wild-type, STAT (signal transducer and activator of transcription)-6-deficient, and IL-4/IL-13-deficient BALB/c mice. Gene profiling of whole lungs was performed, followed by Northern blot and flow cytometric analysis. Anti-CD48, -CD2, and -2B4 antibodies were administered before OVA challenge and cytokine expression and histology were assessed. Measurements and Main Results:Microarray data analysis demonstrated upregulation of CD48 in the lungs of OVA-challenged mice. Allergen-induced CD48 expression was independent of STAT-6, IL-13, and IL-4. Neutralization of CD48 in allergen-challenged mice abrogated bronchoalveolar lavage fluid and lung inflammation. Neutralization of CD2 inhibited the inflammatory response to a lesser extent and neutralization of 2B4 had no effect. Conclusions: Our results suggest that CD48 is critically involved in allergic eosinophilic airway inflammation. As such, CD48 may provide a new potential target for the suppression of asthma.

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“…Given the influence of cytokines on HSC function, we chose to examine the cytokine levels of the CD48 Ϫ/Ϫ BM environment. 9,22,23 After normalizing the cytokine levels to protein levels, the cytokine concentrations of young WT (n ϭ 12) and CD48-null (n ϭ 10) mice were compared. When analyzed as a group, a significant reduction in overall cytokine levels was observed (P Ͻ .01, supplemental Figure 3), with IFN␥ and Cxcl9 presenting individually significant reductions in the CD48 Ϫ/Ϫ supernatant ( Figure 4A).…”

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confidence: 99%

CD48 on hematopoietic progenitors regulates stem cells and suppresses tumor formation

Boles

Lin

Lukov

et al. 2011

Blood

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The proliferation and differentiation of adult stem cells is balanced to ensure adequate generation of differentiated cells, stem cell homeostasis, and guard against malignant transformation. CD48 is broadly expressed on hematopoietic cells but excluded from quiescent longterm murine HSCs. Through its interactions with CD244 on progenitor cells, it influences HSC function by altering the BM cytokine milieu, particularly IFN␥. In CD48-null mice, the resultant misregulation of cytokine signaling produces a more quiescent HSC, a disproportionate number of short-term progenitors, and hyperactivation of Pak1, leading to hematologic malignancies similar to those found in patients with X-linked lymphoproliferative disease. CD48 plays a vital role as an environmental sensor for regulating HSC and progenitor cell numbers and inhibiting tumor development. (Blood. 2011;118(1):80-87) IntroductionHSCs maintain lifelong blood production, but the mechanisms regulating them remain largely obscure. Although several genes have been identified that play key cell-autonomous roles in the HSC, [1][2][3][4] we still have few insights into the manner in which the BM milieu impacts HSC function. Under normal circumstances, the majority of HSCs reside in a quiescent state, with less than 5% in cycle at any given time. 5,6 Nevertheless, blood homeostasis is exquisitely effective, in that the progenitor pool and numbers of differentiated blood cells are maintained at a constant level. To ensure coordinated blood cell production, a sensitive feedback mechanism must be in place, so that the number of progeny are sensed by more primitive progenitors allowing for subtle regulation of the HSCs to generate more downstream cells only as needed. Moreover, under hematopoietic stress, the manufacture of differentiated cells is rapidly adjusted, marshaling increased output from both committed progenitors as well as HSCs. 7 When the loss of blood cells and committed progenitors is particularly complete, virtually all of the HSCs are transiently drafted, after which most of them return to quiescence to ensure long-term maintenance of the HSC pool. 6 CD48 was previously identified as broadly expressed on differentiated hematopoietic cells, but excluded from quiescent long-term HSCs (LT-HSCs). 3,8 CD48 is a GPI-linked member of the signaling lymphocyte activation molecule (SLAM) family of proteins. It can act as a ligand for SLAM member CD244 and, depending on the context, either inhibits or stimulates IFN␥ production from the target cell. 9-12 IFN␥ has previously been shown it to be a suppressor of hematopoiesis and at high levels it may lead to BM failure. 13 However, IFN␥ has also been shown to stimulate progenitor cell proliferation. [14][15][16] Recently, work from our laboratory has shown a lack of IFN␥ in vivo leads to a less proliferative HSC, whereas increasing IFN␥ increases HSC proliferation. 7 Because CD48 offered a context-dependent mechanism for the secretion of IFN␥, which impinges directly on HSCs, we sought to determine its role in maint...

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Functional Role Played by the Glycosylphosphatidylinositol Anchor Glycan of CD48 in Interleukin-18-induced Interferon-γ Production

Cited by 25 publications

References 31 publications

2B4/CD48-Mediated Regulation of Lymphocyte Activation and Function

2B4/CD48-Mediated Regulation of Lymphocyte Activation and Function

CD48 Is Critically Involved in Allergic Eosinophilic Airway Inflammation

CD48 on hematopoietic progenitors regulates stem cells and suppresses tumor formation

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