CS1 (SLAMF7) inhibits production of proinflammatory cytokines by activated monocytes

Kim, Jongrok; Horton, Nathan; Mathew, Stephen O.; Mathew, Porunelloor A.

doi:10.1007/s00011-013-0632-1

Cited by 39 publications

(35 citation statements)

References 51 publications

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“…Additionally, increased expression of Timp1 has been found to attenuate inflammation in endothelium;40 Lyz2 has been implicated in reduction of Il1β, Il6, Tnfα, and Ccl2 production in human ECs;41 Slamf7 has been shown to inhibit the production of proinflammatory cytokines42. The increased gene expression of Timp1, Lyz2, Slamf7, and Alox5ap 24 hrs following FUS (Table 2) may contribute to the observed reduction in cytokine/chemokine gene expression, may reduce EC activation, and may mediate a resolution of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Acute effects of focused ultrasound-induced increases in blood-brain barrier permeability on rat microvascular transcriptome

McMahon

Bendayan

Hynynen

2017

Sci Rep

103

106

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Therapeutic treatment options for central nervous system diseases are greatly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), in conjunction with circulating microbubbles, can be used to induce a targeted and transient increase in BBB permeability, providing a unique approach for the delivery of drugs from the systemic circulation into the brain. While preclinical research has demonstrated the utility of FUS, there remains a large gap in our knowledge regarding the impact of sonication on BBB gene expression. This work is focused on investigating the transcriptional changes in dorsal hippocampal rat microvessels in the acute stages following sonication. Microarray analysis of microvessels was performed at 6 and 24 hrs post-FUS. Expression changes in individual genes and bioinformatic analysis suggests that FUS may induce a transient inflammatory response in microvessels. Increased transcription of proinflammatory cytokine genes appears to be short-lived, largely returning to baseline by 24 hrs. This observation may help to explain some previously observed bioeffects of FUS and may also be a driving force for the angiogenic processes and reduced drug efflux suggested by this work. While further studies are necessary, these results open up intriguing possibilities for novel FUS applications and suggest possible routes for pharmacologically modifying the technique.

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Section: Discussionmentioning

confidence: 99%

Acute effects of focused ultrasound-induced increases in blood-brain barrier permeability on rat microvascular transcriptome

McMahon

Bendayan

Hynynen

2017

Sci Rep

103

106

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“…44,45 Conversely, SLAMF7, a member of the signaling lymphocyte activation molecule family may dampen inflammatory responses in mononuclear phagocytes. 46 Finally, 4 of the genes may promote cell proliferation and survival (Apbb2, Mef2c, Akt3, Ifi205).…”

Section: Gene Expression Differences Between Host-and Donor-derived Amsmentioning

confidence: 99%

Transcriptome analysis highlights the conserved difference between embryonic and postnatal-derived alveolar macrophages

Gibbings

Goyal

Desch³

et al. 2015

Blood

184

176

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• Of the 30 000 genes, there are ;0.1% genes whose expression is linked to the origin of the cell rather than the environment.• Marco was most conserved by embryonic origin and not altered by the environment, whereas C1qb and Plbd1 were most conserved by adult origin.Alveolar macrophages (AMs) reside on the luminal surfaces of the airways and alveoli where they maintain host defense and promote alveolar homeostasis by ingesting inhaled particulates and regulating inflammatory responses. Recent studies have demonstrated that AMs populate the lungs during embryogenesis and self-renew throughout life with minimal replacement by circulating monocytes, except under extreme conditions of depletion or radiation injury. Here we demonstrate that on a global scale, environment appears to dictate AM development and function. Indeed, transcriptome analysis of embryonic host-derived and postnatal donor-derived AMs coexisting within the same mouse demonstrated >98% correlation and overall functional analyses were similar. However, we also identified several genes whose expression was dictated by origin rather than environment. The most differentially expressed gene not altered by environment was Marco, a gene recently demonstrated to have enhancer activity in embryonic-derived but not postnatal-derived tissue macrophages. Overall, we show that under homeostatic conditions, the environment largely dictates the programming and function of AMs, whereas the expression of a small number of genes remains linked to the origin of the cell. (Blood. 2015;126(11):1357-1366 Introduction Alveolar macrophages (AMs) reside on the luminal surfaces of the airways and airspaces where they serve critical roles in host defense and alveolar homeostasis, ingesting particulates and microbes that are constantly encountered in the lungs. Importantly, under most circumstances the phagocytosis of inhaled foreign agents is silent, such that inflammatory responses are activated only under circumstances when host defenses become overwhelmed.1 Indeed, compared with macrophages from other sites, AMs are relatively ineffective at initiating immune responses.2,3 Furthermore, compared with other tissue macrophages, they display a unique repertoire of cell surface molecules and have a distinct transcriptome profile. [4][5][6] AMs are now known to derive primarily from fetal liver monocytes and self-renew throughout life with minimal replenishment from circulating monocytes. [7][8][9][10][11][12][13][14][15] This self-renewal is not only maintained under steady-state conditions, but also during acute and chronic inflammation.16 These concepts were illustrated in lung-protected bone marrow (BM) chimera studies in which lead shields were used to protect AMs during radiation. Eight weeks after BM transplantation, the lungs of these chimeras contained AMs of host origin, whereas circulating monocytes were donor-derived. 16 In these chimeric mice, we showed that during inflammation (lipopolysaccharide or influenza A infection), BM donor-derived monocytes were rapidly...

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“…[5][6][7] SLAMF7 is also present on subsets of monocytes, macrophages, and dendritic cells. 8,9 In the life cycle of normal B cells, SLAMF7 is highly expressed in pro-B cells and plasma cells, and high-level expression is retained in malignant plasma cells in multiple myeloma and its antecedent, "premalignant" stages: monoclonal gammopathy of undetermined significance and smoldering myeloma. [10][11][12] The functional role of SLAMF7 in myeloma pathogenesis is incompletely understood, but several lines of evidence suggest a role in myeloma cell survival and interaction with stroma cells in the bone marrow niche.…”

Section: Introductionmentioning

confidence: 99%

SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7+ normal lymphocytes

Gogishvili

Danhof

Prommersberger

et al. 2017

Blood

170

124

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SLAMF7 is under intense investigation as a target for immunotherapy in multiple myeloma. In this study, we redirected the specificity of T cells to SLAMF7 through expression of a chimeric antigen receptor (CAR) derived from the huLuc63 antibody (elotuzumab) and demonstrate that SLAMF7-CAR T cells prepared from patients and healthy donors confer potent antimyeloma reactivity. We confirmed uniform, high-level expression of SLAMF7 on malignant plasma cells in previously untreated and in relapsed/refractory (R/R) myeloma patients who had received previous treatment with proteasome inhibitors and immunomodulatory drugs. Consequently, SLAMF7-CAR T cells conferred rapid cytolysis of previously untreated and R/R primary myeloma cells in vitro. In addition, a single administration of SLAMF7-CAR T cells led to resolution of medullary and extramedullary myeloma manifestations in a murine xenograft model in vivo. SLAMF7 is expressed on a fraction of normal lymphocytes, including subsets of natural killer (NK) cells, T cells, and B cells. After modification with the SLAMF7-CAR, both CD8 and CD4 T cells rapidly acquired and maintained a SLAMF7 phenotype and could be readily expanded to therapeutically relevant cell doses. We analyzed the recognition of normal lymphocytes by SLAMF7-CAR T cells and show that they induce selective fratricide of SLAMF7 NK cells, CD4 and CD8 T cells, and B cells. Importantly, however, the fratricide conferred by SLAMF7-CAR T cells spares the SLAMF7 fraction in each cell subset and preserves functional lymphocytes, including virus-specific T cells. In aggregate, our data illustrate the potential use of SLAMF7-CAR T-cell therapy as an effective treatment against multiple myeloma and provide novel insights into the consequences of targeting SLAMF7 for the normal lymphocyte compartment.

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CS1 (SLAMF7) inhibits production of proinflammatory cytokines by activated monocytes

Abstract: Our study demonstrated that CS1 plays an inhibitory role in human monocytes to control proinflammatory immune responses.

Cited by 39 publications

References 51 publications

Acute effects of focused ultrasound-induced increases in blood-brain barrier permeability on rat microvascular transcriptome

Acute effects of focused ultrasound-induced increases in blood-brain barrier permeability on rat microvascular transcriptome

Transcriptome analysis highlights the conserved difference between embryonic and postnatal-derived alveolar macrophages

SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7+ normal lymphocytes

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