Cell–cell adhesion mediated by ICAM-1 and VCAM-1 is critical for T cell activation and leukocyte recruitment to the inflammation site and, therefore, plays an important role in evoking effective immune responses. However, we found that ICAM-1 and VCAM-1 were critical for mesenchymal stem cell (MSC)-mediated immunosuppression. When MSCs were cocultured with T cells in the presence of T cell Ag receptor activation, they significantly upregulated the adhesive capability of T cells due to the increased expression of ICAM-1 and VCAM-1. By comparing the immunosuppressive effect of MSCs toward various subtypes of T cells and the expression of these adhesion molecules, we found that the greater expression of ICAM-1 and VCAM-1 by MSCs, the greater the immunosuppressive capacity that they exhibited. Furthermore, ICAM-1 and VCAM-1 were found to be inducible by the concomitant presence of IFN-γ and inflammatory cytokines (TNF-α or IL-1). Finally, MSC-mediated immunosuppression was significantly reversed in vitro and in vivo when the adhesion molecules were genetically deleted or functionally blocked, which corroborated the importance of cell–cell contact in immunosuppression by MSCs. Taken together, these findings reveal a novel function of adhesion molecules in immunoregulation by MSCs and provide new insights for the clinical studies of antiadhesion therapies in various immune disorders.

/pdf/inflammatory-cytokine-induced-intercellular-adhesion-1vq4k2mtsp.pdf

Inflammatory Cytokine-Induced Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 in Mesenchymal Stem Cells Are Critical for Immunosuppression

Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management.

https://jamanetwork.com/journals/jamaophthalmology/articlepdf/1106543/emo110001_90_100.pdf

Dry eye disease: an immune-mediated ocular surface disorder.

Members of the DEWS Research Subcommittee reviewed research into the basic mechanisms underlying dry eye disease. Evidence was evaluated concerning the tear film, lacrimal gland and accessory lacrimal glands, ocular surface epithelia (including cornea and conjunctiva), meibomian glands, lacrimal duct system and the immune system. Consideration was given to both animal and human research data. Results are presented as a series of information matrices, identifying what is known and providing supporting references. An attempt is made to identify areas for further investigation.

Research in dry eye: Report of the research subcommittee of the international Dry Eye WorkShop (2007)

Purpose:Despite extensive knowledge gained over the last 3 decades regarding limbal stem cell deficiency (LSCD), the disease is not clearly defined, and there is lack of agreement on the diagnostic criteria, staging, and classification system among treating physicians and research scientists working

Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency.

Lacrimo-auriculo-dento-digital syndrome [LADD (MIM 149730)] is an autosomal-dominant multiple congenital anomaly disorder characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary systems, cup-shaped ears, hearing loss, and dental and digital anomalies. Loss of function mutations in FGF10 were recently described in aplasia of the lacrimal and salivary glands [ALSG (MIM 180920; MIM 103420)] (Entesarian et al., Nat Genet 2005: 37: 125-127, Milunsky et al., American College of Medical Genetics Annual Meeting, Dallas, TX, 2005: A100). Due to the significant phenotypic overlap between LADD syndrome and ALSG and the variable expressivity of both the disorders, we hypothesized that FGF10 mutations could also result in LADD syndrome. A de novo missense mutation was found in exon 3 of FGF10 in a 3-year-old female (Family 1) with LADD syndrome. This missense mutation, resulting in a non-conservative amino acid change, was confirmed by restriction enzyme digestion and was not found in 500 control chromosomes. A nonsense mutation was also found in exon 2 of FGF10 (Family 2) in a 19-year-old mother with ALSG and her 2-year-old daughter with LADD syndrome. Previous studies of FGF10 mutant mice have demonstrated abnormalities consistent with ALSG and LADD syndrome. We conclude that ALSG and LADD syndrome may represent variable presentations of the same clinical spectrum caused by FGF10 mutations.

LADD syndrome is caused by FGF10 mutations.

PurposeTo correlate conjunctival intercellular adhesion molecule 1 (ICAM-1) expression with cytologic and clinical findings of chronic graft-versus-host disease (GVHD).MethodsSeven patients with ch...

Upregulation of ICAM-1 Expression in the Conjunctiva of Patients with Chronic Graft-Versus-Host Disease:

absence of a highly cellular marrowlike appearance and by the presence of a predominantly sclerotic background. It is believed that myelofibrosis results from a proliferation of polyclonal fibroblasts that is secondary to cytokines released from clonal megakaryocytes or platelets. The orbita is not a typical site for hematopoiesis in either fetuses or adults, and the cause of SEMHT in the orbita is unknown. It has been postulated that circulating stem cells are increased in the peripheral blood of patients with myelofibrosis. These stem cells may deposit in peripheral organs via adhesion integrin molecules and may give rise to ectopic hematopoietic foci. Although our patient developed orbital masses after splenectomy, it is not clear whether the formation of SEMHTs is related to splenectomy. Splenectomy may not be an important factor in the formation of SEMHTs. Moreover, splenectomy is commonly performed in patients with myelofibrosis, but the development of SEMHTs is relatively rare. Althoughthe initial imaging looks alarming, as of this writing, our patient’s disease has had a relatively benigncourse.Theremainingorbital lesionshavebeenmoreor less thesame forthepast3years,asserialcomputed tomographyhasshownnosignificant changes. In addition, the patient’s vision has remained stable. These findings suggest a benign disease. In summary, this is the first reported case, to our knowledge, of SEMHT in the orbitae. Sclerosing extramedullary hematopoietic tumors can histologically and radiologically mimic other soft tissue neoplasms. History of a myeloproliferative disorder and a high index of suspicion are important in making the diagnosis. The clinical course is relatively benign, and aggressive local therapy does not seem to be mandatory.

S. Aronni

Papers

Upregulation of ICAM-1 Expression in the Conjunctiva of Patients with Chronic Graft-Versus-Host Disease:

Limbal Stem Cells Deficiency Associated with LADD Syndrome