The protease cathepsin L regulates Th17 cell differentiation

Journal of Autoimmunity
Lifei HouEileen Remold-O'Donnell

Abstract

Previously we reported that IL-17(+) T cells, primarily IL-17(+) γδ cells, are increased in mice lacking the protease inhibitor serpinB1 (serpinb1(-/-) mice). Here we show that serpinB1-deficient CD4 cells exhibit a cell-autonomous and selective deficiency in suppressing T helper 17 (Th17) cell differentiation. This suggested an opposing role for one or more protease in promoting Th17 differentiation. We found that several SerpinB1-inhibitable cysteine cathepsins are induced in Th17 cells, most prominently cathepsin L (catL); this was verified by peptidase assays, active site labeling and Western blots. Moreover, Th17 differentiation was suppressed by both broad cathepsin inhibitors and catL selective inhibitors. CatL is present in Th17 cells as single chain (SC)- and two-chain (TC)-forms. Inhibiting asparagine endopeptidase (AEP) blocked conversion of SC-catL to TC-catL and increased generation of serpinb1(-/-) Th17 cells, but not wild-type Th17 cells. These findings suggest that SC-catL is biologically active in promoting Th17 generation and is counter-regulated by serpinB1 and secondarily by AEP. Thus, in addition to regulation by cytokines and transcription factors, differentiation of CD4 cells to Th17 cells is actively reg...Continue Reading

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Citations

May 10, 2020·European Journal of Immunology·Shoba Amarnath, Marnie L Brown
Mar 17, 2017·Clinical Reviews in Allergy & Immunology·Andrea T BorchersM Eric Gershwin
Aug 27, 2017·Seminars in Immunopathology·Justin KillickAnne L Astier
Jun 13, 2020·Cell Biochemistry and Function·Song ParkSeong-Kyoon Choi
Sep 27, 2019·Frontiers in Immunology·Tanja JakošJanko Kos
Sep 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Lifei HouEileen Remold-O'Donnell
Jul 15, 2017·Journal of Immunology Research·Shikui XuChunping Wan
Jul 9, 2020·Cells·Anna SałkowskaMarcin Ratajewski
Jan 12, 2020·Biochimica Et Biophysica Acta. Proteins and Proteomics·Xian ZhangGuo-Ping Shi
Feb 5, 2021·International Immunopharmacology·Miho Shibamura-FujiogiLifei Hou
Feb 3, 2021·The FEBS Journal·Biaolong DengBin Li
Feb 19, 2017·Biochemical and Biophysical Research Communications·Charaf Benarafa, Hans-Uwe Simon
Aug 28, 2021·International Journal of Molecular Sciences·Milica Perišić NanutJanko Kos

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