Biology subjects

Yalavarthi, B.

Publications and source records attributed to Yalavarthi, B..

2 recordsLinked to original sources

bioRxiv2026

Targeting activated IL-23 signaling in Scleroderma by tildrakizumab

The pathogenesis of systemic sclerosis (SSc) involves immune system dysregulation and progressive multi-organ fibrosis. Aberrant interleukin-23 (IL-23) function is linked to many inflammatory conditions. Tildrakizumab, a humanized monoclonal antibody that binds to the p19 subunit of IL-23 to block its interaction with the IL-23 receptor, is FDA-approved for treating psoriasis. IL-23 levels are increased in SSc patients with lung involvement, but the pathogenic role of IL-23 in SSc fibrosis remains unclear. We examined IL-23 expression in SSc skin biopsies and assessed the effects of IL-23 inhibition in an in vivo fibrosis model. We found increased IL-23 expression in SSc compared to healthy skin biopsies. Pharmacological blockade of IL-23 signaling using tildrakizumab reversed experimental skin and lung fibrosis. Our findings support a pathogenic role of IL-23 in SSc and suggest that tildrakizumab could be a novel antifibrotic treatment strategy for SSc and related fibrotic disorders. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/701821v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@777c8aorg.highwire.dtl.DTLVardef@9163f5org.highwire.dtl.DTLVardef@1399a54org.highwire.dtl.DTLVardef@c30ec2_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Morphological Reprogramming of Primary Cilia Length Mitigates the Fibrotic Phenotype in fibroblasts across diverse fibrotic conditions

Fibrosis is a hallmark of systemic sclerosis (SSc) and many diverse and incurable diseases. Myofibroblast activation, a common cellular phenomenon shared across fibrotic diseases, is marked by actin polymerization known to affect primary cilia (PC) length. We discovered that fibroblasts from diverse fibrotic conditions display significantly reduced PC length ex vivo. Treatment of healthy fibroblasts with profibrotic TGF-{beta}1 induced PC shortening, while silencing ACTA2 in SSc skin fibroblasts caused PC elongation. Importantly, we found that PC length is negatively correlated with cellular expression of -SMA in TGF-{beta}1-stimulated healthy fibroblasts, or pharmacologically de-differentiated myofibroblasts. PC elongation by microtubule polymerization induction in SSc skin fibroblasts using LiCl or the HDAC6 inhibitor tubacin, reversed and mitigated fibrotic responses. Our results implicate a key role for microtubule polymerization in restraining fibrotic responses and suggest that modulation of PC dynamics may represent a potential therapeutic strategy for SSc and other treatment-resistant diseases associated with fibrosis. Teaser. PC length shortening is a hallmark of fibrosis.

cell biology↗