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Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice

Cooley, Lauren Folgosa ; Martin, Rebecca K ; Zellner, Hannah B ; Irani, Anne-Marie ; Uram-Tuculescu, Cora ; El Shikh, Mohey Eldin ; Conrad, Daniel H Moser, Muriel

PloS one, 2015-05, Vol.10 (5), p.e0124331 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice
Autor: Cooley, Lauren Folgosa ; Martin, Rebecca K ; Zellner, Hannah B ; Irani, Anne-Marie ; Uram-Tuculescu, Cora ; El Shikh, Mohey Eldin ; Conrad, Daniel H
Moser, Muriel
Assuntos: ADAM Proteins - metabolism ; ADAM10 Protein ; ADAM17 Protein ; Allergies ; Amyloid Precursor Protein Secretases - metabolism ; Animals ; Asthma ; B cells ; B-Lymphocytes - immunology ; Bronchoconstriction ; CD23 antigen ; CD40 antigen ; Cellular manufacture ; Comparative analysis ; Dendritic cells ; Disease ; Gene Deletion ; Goblet Cells - pathology ; House dust ; House mouse ; Humans ; Hypersensitivity ; Hypersensitivity - immunology ; Hypersensitivity - pathology ; Hypersensitivity - physiopathology ; Immunoglobulin E ; Immunoglobulin E - immunology ; Immunology ; Infiltration ; Inflammation ; Interleukin 4 ; Kinases ; Laboratories ; Lungs ; Lymphocytes B ; Lymphocytes T ; Lymphoid tissue ; Lymphoid Tissue - metabolism ; Membrane Proteins - metabolism ; Metaplasia ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mucus ; Mucus - metabolism ; Patients ; Pyroglyphidae ; Receptors, IgE - metabolism ; Respiratory tract ; Rodents ; Studies ; Symptomology ; T cells ; Th2 Cells - immunology ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-TNF
É parte de: PloS one, 2015-05, Vol.10 (5), p.e0124331
Notas: Conceived and designed the experiments: LFC MEES DHC. Performed the experiments: LFC RKM HBZ. Analyzed the data: LFC RKM MEES DHC CUT. Contributed reagents/materials/analysis tools: MEES DHC. Wrote the paper: LFC MEES DHC. Edited manuscript: LFC RKM HBZ AMI MEES DHC CUT.
Competing Interests: The authors have declared that no competing interests exist.
These authors are joint senior authors this work.
Descrição: ADAM10, as the sheddase of the low affinity IgE receptor (CD23), promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J). While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone) WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J) compared to Th1 prone controls. To further understand this regulation, ADAM17 and TNF were studied in C57Bl/6 and Balb/c mice deficient in ADAM10. C57-ADAM10B-/- were more adept at increasing ADAM17 levels and thus TNF cleavage resulting in excess follicular TNF levels and abnormal secondary lymphoid tissue architecture not noted in Balb-ADAM10B-/-. Moreover, the level of B cell ADAM10 as well as Th context is critical for determining IgE production potential. Using a murine house dust mite airway hypersensitivity model, we describe that high B cell ADAM10 level in a Th2 context (Balb/c WT) is optimal for disease induction including bronchoconstriction, goblet cell metaplasia, mucus, inflammatory cellular infiltration, and IgE production. Balb/c mice deficient in B cell ADAM10 have attenuated lung and airway symptoms compared to Balb WT and are actually most similar to C57 WT (Th1 prone). C57-ADAM10B-/- have even further reduced symptomology. Taken together, it is critical to consider both innate B cell levels of ADAM10 and ADAM17 as well as Th context when determining host susceptibility to allergic disease. High B cell ADAM10 and low ADAM17 levels would help diagnostically in predicting Th2 disease susceptibility; and, we provide support for the use ADAM10 inhibitors in treating Th2 disease.
Editor: United States: Public Library of Science
Idioma: Inglês

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Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice

Cooley, Lauren Folgosa ; Martin, Rebecca K ; Zellner, Hannah B ; Irani, Anne-Marie ; Uram-Tuculescu, Cora ; El Shikh, Mohey Eldin ; Conrad, Daniel H Moser, Muriel

United States: Public Library of Science

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