168 TLR7-VGLL3 synergism potentiates lupus-like autoimmunity in mice
نویسندگان
چکیده
Many autoimmune diseases exhibit a striking female bias, including systemic lupus erythematosus (SLE), in which patients outnumber male 9 to 1. This skewing may part result from incomplete X chromosome inactivation of immune-related genes, such as Toll-like receptor 7 (TLR7). The mechanisms by TLR7 contributes the development autoimmunity are under active investigation. Our lab previously found that Vestigial Like Family Member 3 (VGLL3), encodes an autosomal putative transcription co-factor implicated female-specific inflammation, induces SLE-like disease when overexpressed epidermal K5 promoter mice. Interestingly, was upregulated 4.5-fold (p<0.01) K5-VGLL3 To evaluate potential genetic interaction between VGLL3 and TLR7, we employed 2 mouse models. First, deletion mice did not arrest or delay skin lesions splenomegaly, but RNA sequencing revealed blunted molecular phenotype kidneys more prominent females corresponded sex differences circulating anti-dsDNA antibodies. Second, treating VGLL3-deficient with agonist resulted dampened inflammation compared WT controls significantly lower induction interferon-dependent MX1 OAS1A, observed transcriptomic shift. Taken together, these data suggest potentiates pro-inflammatory effects acting feedforward loop drives sex-biased interferon-associated manner. Further mechanistic investigations behind TLR7-VGLL3 synergism underway our lab.
منابع مشابه
A Tlr7 translocation accelerates systemic autoimmunity in murine lupus.
The y-linked autoimmune accelerating (yaa) locus is a potent autoimmune disease allele. Transcription profiling of yaa-bearing B cells revealed the overexpression of a cluster of X-linked genes that included Tlr7. FISH analysis demonstrated the translocation of this segment onto the yaa chromosome. The resulting overexpression of Tlr7 increased in vitro responses to Toll-like receptor (TLR) 7 s...
متن کاملGalectin-9 inhibits TLR7-mediated autoimmunity in murine lupus models.
Uncontrolled secretion of type I IFN, as the result of endosomal TLR (i.e., TLR7 and TLR9) signaling in plasmacytoid DCs (pDCs), and abnormal production of autoantibodies by B cells are critical for systemic lupus erythematosus (SLE) pathogenesis. The importance of galectin-9 (Gal-9) in regulating various autoimmune diseases, including lupus, has been demonstrated. However, the precise mechanis...
متن کاملImpaired T Cell Death and Lupus-like Autoimmunity in T Cell–specific Adapter Protein–deficient Mice
T cell-specific adaptor protein (TSAd) is a T lineage-restricted signaling adaptor molecule that is thought to participate in the assembly of intracellular signaling complexes in T cells. Previous studies of TSAd-deficient mice have revealed a role for TSAd in the induction of T cell interleukin 2 secretion and proliferation. We now show that TSAd-deficient mice are susceptible to lupus-like au...
متن کاملEffects of MHC and gender on lupus-like autoimmunity in Nba2 congenic mice.
The lupus-like disease that develops in hybrids of NZB and NZW mice is genetically complex, involving both MHC- and non-MHC-encoded genes. Studies in this model have indicated that the H2d/z MHC type, compared with H2d/d or H2z/z, is critical for disease development. C57BL/6 (B6) mice (H2b/b) congenic for NZB autoimmunity 2 (Nba2), a NZB-derived susceptibility locus on distal chromosome 1, prod...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2023
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2023.03.169