Open AccessThe role of ADAM17 in the T-cell response against bacterial pathogens
Author(s) -
Moritz Andreas Link,
Karsten Lücke,
Joanna Schmid,
Valéa Schumacher,
Thomas Watts Eden,
Stefan Rose-John,
HansWilli Mittrücker
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0184320
Subject(s) - biology , t cell , proteases , listeria monocytogenes , microbiology and biotechnology , immune system , cd8 , disintegrin , effector , cytokine , cytotoxic t cell , immunology , metalloproteinase , genetics , matrix metalloproteinase , in vitro , bacteria , biochemistry , enzyme
ADAM17 is a member of the A Disintegrin And Metalloproteinase family of proteases. It is ubiquitously expressed and causes the shedding of a broad spectrum of surface proteins such as adhesion molecules, cytokines and cytokine receptors. By controlled shedding of these proteins from leukocytes, ADAM17 is able to regulate immune responses. Several ADAM17 targets on T cells have been implicated in T-cell migration, differentiation and effector functions. However, the role of ADAM17 in T-cell responses is still unclear. To characterize the function of ADAM17 in T cells, we used Adam17 fl/fl × CD4cre + mice with a T-cell restricted inactivation of the Adam17 gene. Upon stimulation, ADAM17-deficient CD4 + and CD8 + T cells were impaired in shedding of CD62L, IL-6Rα, TNF-α, TNFRI and TNFRII. Surprisingly, we could not detect profound changes in the composition of major T-cell subsets in Adam17 fl/fl × CD4cre + mice. Following infection with Listeria monocytogenes , Adam17 fl/fl × CD4cre + mice mounted regular listeria-specific CD4 + T H1 and CD8 + T-cell responses and were able to control primary and secondary infections. In conclusion, our study indicates that ADAM17 is either not required in T cells under homoeostatic conditions and for control of listeria infection or can be effectively compensated by other mechanisms.