Biology subjects

Musaigwa, F.

Publications and source records attributed to Musaigwa, F..

3 recordsLinked to original sources

bioRxiv2026

Sensory neurons shape γδ T cell effector programs to control Psoriasiform Inflammation.

Psoriasis is a chronic autoimmune skin disorder marked by IL-17 producing gamma delta T cell ({gamma}{delta}T17) and pruritus, but immunoregulatory roles of itch-inducing neurons in this context remain unclear. This study addressed whether non-peptidergic (NP) afferents bearing the Mas-related G protein-coupled receptor D (MrgprD/NP1) and MrgprA3/NP2 subsets had differential effects on psoriasiform immunopathology. Data show human NP1 and NP2 neurons basally expressed an array of pattern recognition and cytokine receptor genes and psoriatic human skin had a profound dysregulation of neuropeptides and their receptors. In mice, imiquimod (IMQ) application reduced the density of MrgprD+ skin afferents, whereas NP1 neuron ablation exacerbated IMQ-induced disease. Strikingly, NP1 activation using either optogenetics or {beta}-alanine before IMQ exposure significantly reduced epidermal thickness, psoriatic clinical score and {gamma}{delta}T17 cell accumulation. In stark contrast, NP2 activation increased the numbers of {gamma}{delta}T17 cells that co-expressed amphiregulin (Areg) and exacerbated IMQ-driven skin pathology. Instead, pre-emptive NP1 stimulation shifted {gamma}{delta} T cell profiles away from being IL-17 and Areg dominant to IL-13+ {gamma}{delta} T cells expressing the transcription factor GATA3 accompanied by IL-10 secretion. Importantly, IL-10 signaling blockade reversed NP1-mediated suppression of IMQ-induced dermatitis. These data show that inflammatory skin disease can be distinctly modulated by sensory neuron subsets.

immunology↗

bioRxiv2025

Trained ILC2 prevent IL-17-associated lung injury during helminth infection through a serotonin-dependent mechanism

Type 2 cytokine release promotes wound healing and helminth clearance, but it remains unclear whether group 2 innate lymphocytes (ILC2s) and T-helper 2 cells (TH2) cells have functionally distinct roles during anamnestic immunity. This study demonstrates that ILC2 can block re-infection and limit tissue injury caused by the helminth Nippostrongylus brasiliensis (Nb). TH2 cells were necessary during initial antigen encounter but dispensable for pathogen clearance and lung repair after ILC2 priming. Upon re-infection, trained ILC2 selectively blocked interleukin (IL)-17+ {gamma}{delta}T cell expansion and infection-induced lung injury through an Amphiregulin (Areg)-independent mechanism. Trained ILC2s had a distinct metabolic gene expression profile marked by elevated tryptophan hydroxylase 1(Tph1) and pulmonary serotonin levels were largely ILC2-dependent. Surprisingly, serotonin prevented IL-17-associated lung hemorrhage irrespective of parasite load. We propose that TH2-ILC2 interactions drive pathogen control, but ILC2 distinctly control lung tissue repair through serotonin.

immunology↗

bioRxiv2023

Immunoglobulin M regulates airway hyperresponsiveness independent of T helper 2 allergic inflammation.

Allergic asthma is a disease driven by T helper 2 (Th2) cells, eosinophilia, airway hyperresponsiveness (AHR) and IgE-secreting B cells. Asthma is largely controlled by corticosteroids and {beta}2 adregenic receptor agonists that target and relax airway smooth muscle (ASM). Immunoglobulin M (IgM) isotype secreted by naive B cells is important for class switching but may have other undefined functions. We investigated the role of IgM in a house dust mite (HDM)-induced Th2 allergic asthma model. We sensitised wild-type (WT) and IgM-deficient (IgM KO) mice with HDM and measured AHR, and Th2 responses. We performed RNA sequencing on the whole lung of WT and IgM KO mice sensitised to saline or HDM. We validated our AHR data on human ASM by deleting genes using CRISPR and measuring contraction by single-cell force cytometry. We found IgM to be essential in AHR but not Th2 airway inflammation or eosinophilia. RNA sequencing of lung tissue suggested that IgM regulated AHR through modulating brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (Baiap2l1) and other genes. Deletion of BAIAP2L1 led to a differential reduction in human ASM contraction when stimulated with TNF- and Acetylcholine, but not IL-13. These findings have implications for future treatment of asthma beyond current therapies.

immunology↗