The initial focus of our studies has been patient populations with severe neutrophil defects. Patients with severe neutropenia or defective neutrophil recruitment into tissues are known to develop severe-aggressive periodontitis at a young age. However, the mechanisms by which tissue neutrophils alter microbial colonization and regulation of mucosal immunity had not been investigated until recently. One such rare patient cohort is that of Leukocyte Deficiency I (LAD-I). LAD-I is an autosomal recessive immunodeficiency caused by mutations in the CD18-encoding ITGB2 gene that result in defective neutrophil adhesion and transmigration. Affected individuals display neutrophilia, suffer from recurrent infections, and invariably develop early-onset generalized aggressive periodontitis featuring severe bone loss and premature loss of primary and permanent teeth. LAD periodontitis historically has been attributed to the lack of neutrophil surveillance leading to periodontal infection. We recently showed for the first time that IL-17 plays a major role in the oral pathology of LAD-I. Defective neutrophil recruitment in LAD-I patients, or in LFA-1 (CD11a/CD18)-deficient mice that have the same periodontal phenotype, was associated with excessive production of T cell-derived IL-17 in the periodontal tissue. Strikingly, local treatment with anti-IL-17 (or anti-IL-23) in LFA-1deficient mice blocked this inflammatory periodontal bone loss. This novel role for IL-17 in the etiology of LAD-I periodontitis has directed my attention to the development of IL-17targeted therapies for severe periodontal disease.
| Abusleme, Loreto; Diaz, Patricia I; Freeman, Alexandra F et al. (2018) Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis. JCI Insight 3: |
| Abusleme, L; Moutsopoulos, N M (2017) IL-17: overview and role in oral immunity and microbiome. Oral Dis 23:854-865 |
| Moutsopoulos, Niki M; Zerbe, Christa S; Wild, Teresa et al. (2017) Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1. N Engl J Med 376:1141-1146 |
| Shah, Nirali N; Freeman, Alexandra F; Su, Helen et al. (2017) Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide. Biol Blood Marrow Transplant 23:980-990 |
| Dutzan, Nicolas; Konkel, Joanne E; Greenwell-Wild, Teresa et al. (2016) Characterization of the human immune cell network at the gingival barrier. Mucosal Immunol 9:1163-1172 |
| Hajishengallis, George; Moutsopoulos, Niki M (2016) Role of bacteria in leukocyte adhesion deficiency-associated periodontitis. Microb Pathog 94:21-6 |
| Falcone, E Liana; Abusleme, Loreto; Swamydas, Muthulekha et al. (2016) Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome. Microbiome 4:13 |
| Cuellar-Rodriguez, Jennifer; Freeman, Alexandra F; Grossman, Jennifer et al. (2015) Matched related and unrelated donor hematopoietic stem cell transplantation for DOCK8 deficiency. Biol Blood Marrow Transplant 21:1037-45 |
| Moutsopoulos, N M; Lionakis, M S; Hajishengallis, G (2015) Inborn errors in immunity: unique natural models to dissect oral immunity. J Dent Res 94:753-8 |
| Moutsopoulos, Niki M; Chalmers, Natalia I; Barb, Jennifer J et al. (2015) Subgingival microbial communities in Leukocyte Adhesion Deficiency and their relationship with local immunopathology. PLoS Pathog 11:e1004698 |
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