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Increased cathepsin S in Prdm1(-/-) dendritic cells alters the T-FH cell repertoire and contributes to lupus

Title
Increased cathepsin S in Prdm1(-/-) dendritic cells alters the T-FH cell repertoire and contributes to lupus
Author
장수화
Keywords
ANTIGEN PRESENTATION; ERYTHEMATOSUS; ALPHA; DIFFERENTIATION; SUSCEPTIBILITY; INFLAMMATION; ACTIVATION; GENERATION; EXPRESSION; RESPONSES
Issue Date
2017-07
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE IMMUNOLOGY, v. 18, no. 9, page. 1016-1024
Abstract
Aberrant population expansion of follicular helper T cells (TFH cells) occurs in patients with lupus. An unanswered question is whether an altered repertoire of T cell antigen receptors (TCRs) is associated with such expansion. Here we found that the transcription factor Blimp-1 (encoded by Prdm1) repressed expression of the gene encoding cathepsin S (Ctss), a cysteine protease that cleaves invariant chains and produces antigenic peptides for loading onto major histocompatibility complex (MHC) class II molecules. The increased CTSS expression in dendritic cells (DCs) from female mice with dendritic cell-specific conditional knockout of Prdm1 (CKO mice) altered the presentation of antigen to CD4(+) T cells. Analysis of complementarity-determining region 3 (CDR3) regions containing the beta-chain variable region (V-beta) demonstrated a more diverse repertoire of T-FH cells from female CKO mice than of those from wild-type mice. In vivo treatment of CKO mice with a CTSS inhibitor abolished the lupus-related phenotype and reduced the diversity of the TFH cell TCR repertoire. Thus, Blimp-1 deficiency in DCs led to loss of appropriate regulation of Ctss expression in female mice and thereby modulated antigen presentation and the T-FH cell repertoire to contribute to autoimmunity.
URI
https://www.nature.com/articles/ni.3793https://repository.hanyang.ac.kr/handle/20.500.11754/114977
ISSN
1529-2908; 1529-2916
DOI
10.1038/ni.3793
Appears in Collections:
RESEARCH INSTITUTE[S](부설연구소) > ETC
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