Activated Leukocyte Cell Adhesion Molecule Stimulates the T-Cell Response in Allergic Asthma

Kim, Seung Up; Hong, Jung Yeon; Shim, Doo Hee; Sol, In Suk; Kim, Yun Seon; Lee, Ji Hyun; Kim, Kyung Won; Lee, Jae Myun; Sohn, Myung Hyun

doi:10.1164/rccm.201703-0532oc

Cited by 23 publications

(30 citation statements)

References 47 publications

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“…FACS analysis confirmed constitutive expression of CD6 in CD4 + OTII T cells and of ALCAM in BM-DCs (Figure 2F). Similarly to two recent reports (10, 11), we found that in vitro proliferation (Figures 2G,H) and IFN-γ production (Figure 2I) of OTII T cells were significantly reduced in co-cultures involving ALCAM −/− DCs. Moreover, treatment of co-cultures involving WT DCs with I/F8-Fc reduced T cell proliferation and IFN-γ production to similar levels as observed in co-cultures of T cells and ALCAM −/− DCs (Figures 2H,I).…”

Section: Resultssupporting

confidence: 91%

“…Moreover, ALCAM on DCs interacting with T cell-expressed CD6 was shown to provide T cell co-stimulation in vitro (9). In line with the latter findings, two recent studies reported that ALCAM-deficient (ALCAM −/− ) mice are partially protected from T cell-mediated inflammation in murine models of asthma (10) and food allergy (11). In ECs ALCAM was shown to mediate in vitro migration, tube formation and barrier function of blood vascular and lymphatic ECs (LECs) (2, 12, 13).…”

Section: Introductionsupporting

confidence: 63%

“…To date no monoclonal antibody with biochemically documented blocking activity toward murine ALCAM has been described. Treatment with polyclonal goat anti-mouse ALCAM antibody was recently shown to reduce allergic symptoms in a murine asthma model (10), but polyclonal antibodies from other species are not suited for long-term therapies due to immunogenicity. In addition, treatment with a monoclonal mouse IgG 1 raised against human ALCAM was previously reported to reduce the severity of murine experimental autoimmune encephalitis (6), but in our hands this antibody neither blocked nor bound murine ALCAM (Figure S1).…”

Section: Resultsmentioning

confidence: 99%

“…Last but not least, in our in vitro experiments ALCAM blockade also reduced T cell activation by antigen-presenting DCs, likely by interfering with ALCAM-CD6 interactions. Given that ALCAM −/− mice display reduced T cell activation and T cell mediated inflammatory responses in experimental mouse models of antigen-induced food allergy or asthma (10, 11), it is possible that the I/F8-mediated delay in corneal allograft rejection can in part be attributed to direct effects on T cell activation.…”

Section: Discussionmentioning

confidence: 99%

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ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions

et al. 2019

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Activated leukocyte cell adhesion molecule (ALCAM, CD166) is a cell adhesion molecule of the immunoglobulin superfamily and has been implicated in diverse pathophysiological processes including T cell activation, leukocyte trafficking, and (lymph)angiogenesis. However, exploring the therapeutic potential of ALCAM blockade in immune-mediated inflammatory disorders has been difficult due to the lack of antibodies with blocking activity toward murine ALCAM. In this study, we identified and characterized a monoclonal antibody with high affinity and specificity for murine ALCAM. This antibody reduced in vitro T cell activation induced by antigen-presenting dendritic cells (DCs) as well as (trans)migration of murine DCs across lymphatic endothelial monolayers. Moreover, it reduced emigration of DCs from in vitro -cultured human skin biopsies. Similarly, antibody-based blockade of ALCAM reduced (lymph)angiogenic processes in vitro and decreased developmental lymphangiogenesis in vivo to levels observed in ALCAM-deficient mice. Since corneal allograft rejection is an important medical condition that also involves (lymph)angiogenesis, DC migration and T cell activation, we investigated the therapeutic potential of ALCAM blockade in murine corneal disease. Blocking ALCAM lead to DC retention in corneas and effectively prevented corneal allograft rejection. Considering that we also detected ALCAM expression in human corneal DCs and lymphatics, our findings identify ALCAM as a potential novel therapeutic target in human corneal allograft rejection.

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Section: Resultssupporting

confidence: 91%

Section: Introductionsupporting

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions

et al. 2019

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“…Prior studies demonstrated that ALCAM contributes to ovalbumin (OVA)-induced allergic asthma and food allergy by stimulating T-cell activation and proliferation 2829. Although ALCAM is associated with hypersensitivity and T cell activation in the initiation of immune responses, its function in AD has not yet been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Activated Leukocyte Cell Adhesion Molecule Modulates Th2 Immune Response in Atopic Dermatitis

Hong

Kim

et al. 2019

Allergy Asthma Immunol Res

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Purpose Activated leukocyte cell adhesion molecule (ALCAM), a member of the immunoglobulin superfamily, is highly expressed on dendritic cells. ALCAM and its receptor CD6 are co-stimulatory molecules in the immunological synapse; their interaction is required for T cell activation. While atopic dermatitis (AD) is recognized as a T helper 2 (Th2)-mediated allergic disease, the role of ALCAM in its pathogenesis is unclear. Methods ALCAM levels were measured in the serum of AD patients and AD-induced murine model by ovalbumin treatment. We next investigated transepidermal water loss, clinical score, Th2-immune responses, skin barrier gene expression and T-cell activation using wild-type (WT) and ALCAM deficiency mice. An oxazolone-induced AD-like model was also established and analyzed using WT- and ALCAM-deficient mice. Results We found that serum ALCAM levels were elevated in pediatric AD patients as well as WT AD mice, whereas Th2-type cytokine production and AD symptoms were suppressed in ALCAM-deficient mice. In addition, CD4 + effector T-cell counts in murine skin and skin-draining lymph nodes were lower in ALCAM-deficient mice than in their WT counterparts. ALCAM deficiency was also linked to higher expression of skin barrier genes and number of lamellar bodies. Conclusions These findings indicate that ALCAM may contribute to AD pathogenesis by meditating a Th2-dominant immune response and disrupting the barrier function of the skin.

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Activated Leukocyte Cell Adhesion Molecule Regulates the Expression of Interleukin-33 in RSV Induced Airway Inflammation by Regulating MAPK Signaling Pathways

Baek,

Kim,

Kim

et al. 2024

Lung

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Activated Leukocyte Cell Adhesion Molecule Stimulates the T-Cell Response in Allergic Asthma

Abstract: ALCAM contributes to OVA-induced allergic asthma by stimulating T-cell activation and proliferation, suggesting it as a potential therapeutic target for allergic asthma.

Cited by 23 publications

References 47 publications

ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions

ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions

Activated Leukocyte Cell Adhesion Molecule Modulates Th2 Immune Response in Atopic Dermatitis

Activated Leukocyte Cell Adhesion Molecule Regulates the Expression of Interleukin-33 in RSV Induced Airway Inflammation by Regulating MAPK Signaling Pathways

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