Biology subjects

Rocca, Y.

Publications and source records attributed to Rocca, Y..

3 recordsLinked to original sources

bioRxiv2025

Immunological liver-skin axis: a systemic Vγ4+ γδT17 cell responselinks psoriasis-like inflammation and MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) and psoriasis frequently co-occur and share interleukin-17 (IL-17)-mediated inflammatory mechanisms. Using a murine model combining Western-diet-induced early MASLD with chronic imiquimod-triggered psoriasis-like dermatitis, we observed exacerbated skin inflammation with increased cellularity and systemic IL-17-driven immune activation. In mice with psoriasis-like skin inflammation, hepatic {gamma}{delta}T cells shifted from IFN-{gamma}-producing {gamma}{delta}T1 toward IL-17-secreting {gamma}{delta}T17 cells, accompanied by an acute-phase response and induction of hepatic lipogenic gene expression. Single-cell RNA sequencing revealed an expansion of V{gamma}4 {gamma}{delta}T17 cells engaged in IL-17 and TGF-{beta} signaling, consistent with early fibrogenic responses. Together, these findings identify V{gamma}4 {gamma}{delta}T17 cells as a mechanistic link between psoriasis and MASLD, promoting systemic inflammation and early hepatic remodeling. Consistently, in a clinical cohort of patients with moderate-to-severe psoriasis and co-morbid MASLD, IL-17-targeted therapy improved hepatic steatosis, underscoring the translational relevance of this immunological axis.

immunology↗

bioRxiv2023

IL-33 drives polyfunctionality and antitumor activity of a unique ST2+ NK cell population

Despite increasing recognition of NK cell diversity, their functional heterogeneity and its relevance to cancer remain incompletely understood. Here, we show that IL-12 promotes the emergence of a distinct ST2/IL33R+ NK cell state poised for robust activation by IL-33. Human ST2 NK cells exhibit a unique transcriptional program, an intermediate differentiation state between CD56bright and CD56dim NK cells, and enhanced polyfunctionality combining proliferation, cytokine production, and cytotoxicity. ST2 NK cells were identified across human and murine tumor datasets. In murine breast cancer models, IL-33 and IL-12 cooperated to elicit potent antitumor responses dependent on IFN-{gamma} and ST2 NK cells. In cancer patients, IL-12 unleashed tumor-infiltrating ST2 NK cells' potential to produce IFN-g in response to IL-33, an IL33hi-NKhi score was associated with prolonged survival, and ST2 NK cells correlated with improved immunotherapy response. Collectively, these findings identify ST2 NK cells as a therapeutically actionable NK cell state promoting antitumor immunity.

cancer biology↗

bioRxiv2020

Peripheral Natural Killer cells from chronic hepatitis B patients display molecular hallmarks of T cell exhaustion

A significant proportion of individuals infected by HBV develops chronic infection. Antiviral effectors such as Natural Killer (NK) cells have impaired functions in these patients, but the molecular mechanism responsible for this dysfunction remains poorly characterized. Here, we show that peripheral NK cells from chronic hepatitis B (CHB) patients have a defective capacity to produce IFN-{gamma}, MIP1-{beta} and TNF- but retain an intact killing capacity. This functional phenotype was associated with a decrease in the expression of NKp30 and CD16, combined with defects in IL-15 stimulation of the mTOR pathway. Transcriptome analysis of NK cells in CHB patients further revealed a strong enrichment for transcripts typically expressed in exhausted T cells suggesting that NK cell dysfunction and T cell exhaustion rely on common molecular mechanisms. In particular, the transcription factor thymocyte selection-associated HMG box protein (TOX) and several of its targets, including immune checkpoints, were over-expressed in NK cells of CHB patients. This T cell exhaustion signature was predicted to be dependent on the calcium (Ca2+)-associated transcription factor NFAT. In line with this, when stimulating the Ca2+-dependent pathway in isolation, we recapitulated the dysfunctional phenotype. Thus, deregulated Ca2+ signalling could be a central event in both T cell exhaustion and NK cell dysfunction that occur during chronic infections.

immunology↗