Negative regulation of autoimmune demyelination by the inhibitory receptor CLM-1

Xi, Hongkang; Katschke, Kenneth J.; Helmy, Karim Y.; Wark, Peter; Kljavin, Noelyn M.; Clark, Hilary; Eastham-Anderson, Jeffrey; Shek, Theresa; Roose‐Girma, Merone; Ghilardi, Nico; Campagne, Menno van Lookeren

doi:10.1084/jem.20091508

Cited by 52 publications

(76 citation statements)

References 26 publications

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“…16,19,26 In agreement with this findings, blocking of CD300a and PS interactions induces increased inflammatory cytokine production from mast cells, 26 and CD300f deficiency leads to a predispostion to autoimmune disease development, 19 as well as an exacerbation in the allergic responses and autoimmune diseases. 19,25,33,34 In contrast, our data characterize CD300b as a positive regulator of phagocytosis, through its association with DAP12. The exact role of CD300b in efferocytosis remains to be elucidated, but the existing data suggest that CD300b is involved in the regulation of some immune responses.…”

Section: Resultscontrasting

confidence: 67%

CD300b regulates the phagocytosis of apoptotic cells via phosphatidylserine recognition

et al. 2014

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The CD300 receptor family members are a group of molecules that modulate a variety of immune cell processes. We show that mouse CD300b (CLM7/LMIR5), expressed on myeloid cells, recognizes outer membrane-exposed phosphatidylserine (PS) and does not, as previously reported, directly recognize TIM1 or TIM4. CD300b accumulates in phagocytic cups along with F-actin at apoptotic cell contacts, thereby facilitating their engulfment. The CD300b-mediated activation signal is conveyed through CD300b association with the adaptor molecule DAP12, and requires a functional DAP12 ITAM motif. Binding of apoptotic cells promotes the activation of the PI3K-Akt kinase pathway in macrophages, while silencing of CD300b expression diminishes PI3K-Akt kinase activation and impairs efferocytosis. Collectively, our data show that CD300b recognizes PS as a ligand, and regulates the phagocytosis of apoptotic cells via the DAP12 signaling pathway.

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Section: Resultscontrasting

confidence: 67%

CD300b regulates the phagocytosis of apoptotic cells via phosphatidylserine recognition

et al. 2014

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“…55 Besides the SLE-like disease as shown in this study, CD300f deficiency has been shown to contribute to development and pathogenesis of experimental autoimmune encephalomyelitis and colitis in mouse models. 56,57 An intronic SNP (rs10512597) of CD300f has been associated with the etiology of psoriasis disease and possibly with cardiovascular diseases. 58,59 A nonsynonymous SNP (rs2034310) in the region encoding the cytoplasmic part of CD300f has been associated with multiple sclerosis.…”

Section: Resultsmentioning

confidence: 99%

Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice

Tian

Lee

et al. 2016

Cell Death Differ

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Homeostasis requires the immunologically silent clearance of apoptotic cells before they become pro-inflammatory necrotic cells. CD300f (CLM-1) is a phosphatidylserine receptor known to positively regulate efferocytosis by macrophages, and CD300f genedeficient mice are predisposed to develop a lupus-like disease. Here we show that, in contrast to CD300f function in macrophages, its expression inhibits efferocytosis by DC, and its deficiency leads to enhanced antigen processing and T-cell priming by these DC. The consequences are the expansion of memory T cells and increased ANA levels in aged CD300f-deficient mice, which predispose CD300f-deficient mice to develop an overt autoimmune disease when exposed to an overload of apoptotic cells, or an exacerbated autoimmunity when combined with FcγRIIB deficiency. Thus, our data demonstrates that CD300f helps to maintain immune homeostasis by promoting macrophage clearance of self-antigens, while conversely inhibiting DC uptake and presentation of self-antigens.

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“…51 However, these results were not reproduced by others. 77 In another study, it was shown that mouse CD300f-Fc binds to apoptotic cells, suggesting that CD300f also recognizes phospholipids exposed on the outer leaflet of the plasma membrane of dead cells. Indeed, this binding was blocked when the PS ligand annexin V was present in the assay.…”

Section: 76mentioning

confidence: 99%

The CD300 molecules: an emerging family of regulators of the immune system

Borrego

2013

Blood

193

274

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The CD300 family of molecules modulates a broad and diverse array of immune cell processes via their paired activating and inhibitory receptor functions. The description that CD300 molecules are able to recognize lipids, such as extracellular ceramide, phosphatidylserine, and phosphatidylethanolamine, that are exposed on the outer leaflet of the plasma membrane of dead and activated cells has opened a new field of research. Through their binding to lipids and other ligands, this family of receptors is poised to have a significant role in complex biological processes and in the host response to severe pathological conditions. Indeed, published data have demonstrated their participation in the pathogenesis of several disease states. Moreover, this family of receptors has great potential as targets for diagnosis and therapeutic purposes in infectious diseases, allergies, cancer, and other pathological situations. For instance, one member of the family, CD300a, has been studied as a possible biomarker. Here, a review is provided on the cellular distribution of the human and mouse families of receptors, the stimuli that regulate their expression, their ability to tune leukocyte function and immune responses, their signaling pathways, ligand recognition, and their clinical relevance.

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Negative regulation of autoimmune demyelination by the inhibitory receptor CLM-1

Cited by 52 publications

References 26 publications

CD300b regulates the phagocytosis of apoptotic cells via phosphatidylserine recognition

CD300b regulates the phagocytosis of apoptotic cells via phosphatidylserine recognition

Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice

The CD300 molecules: an emerging family of regulators of the immune system

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