Title |
The Metalloprotease ADAM12 Regulates the Effector Function of Human Th17 Cells
|
---|---|
Published in |
PLOS ONE, November 2013
|
DOI | 10.1371/journal.pone.0081146 |
Pubmed ID | |
Authors |
Angela X. Zhou, Aimee El Hed, Frances Mercer, Lina Kozhaya, Derya Unutmaz |
Abstract |
A key modulator of immune homeostasis, TGFβ has an important role in the differentiation of regulatory T cells (Tregs) and IL-17-secreting T cells (Th17). How TGFβ regulates these functionally opposing T cell subsets is not well understood. We determined that an ADAM family metalloprotease called ADAM12 is specifically and highly expressed in both Tregs and CCR6+ Th17 cells. ADAM12 is induced in vitro upon differentiation of naïve T cells to Th17 cells or IL-17-secreting Tregs. Remarkably, silencing ADAM12 expression in CCR6+ memory T cells enhances the production of Th17 cytokines, similar to suppressing TGFβ signaling. Further, ADAM12 knockdown in naïve human T cells polarized towards Th17/Treg cells, or ectopically expressing RORC, greatly enhances IL-17-secreting cell differentiation, more potently then inhibiting TGFβ signals. Together, our findings reveal a novel regulatory role for ADAM12 in Th17 cell differentiation or function and may have implications in regulating their aberrant responses during immune pathologies. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Colombia | 1 | 4% |
United States | 1 | 4% |
Unknown | 21 | 91% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 4 | 17% |
Student > Ph. D. Student | 4 | 17% |
Student > Bachelor | 3 | 13% |
Researcher | 3 | 13% |
Other | 2 | 9% |
Other | 5 | 22% |
Unknown | 2 | 9% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 5 | 22% |
Agricultural and Biological Sciences | 5 | 22% |
Immunology and Microbiology | 4 | 17% |
Medicine and Dentistry | 4 | 17% |
Neuroscience | 2 | 9% |
Other | 1 | 4% |
Unknown | 2 | 9% |