Biology subjects

Taglinao, H.

Publications and source records attributed to Taglinao, H..

3 recordsLinked to original sources

bioRxiv2026

Intestinal intraepithelial lymphocyte migration and tissue homeostasis are dictated by Gα13

Intestinal intraepithelial lymphocytes (IEL), including conventional CD8{beta} T resident memory (Trm) cells and unconventional CD8 T cells, promote tissue integrity. Here, we studied the G-protein coupled receptor signals regulating IEL positioning, homeostasis, and function. Deficiency in heterotrimeric G-protein subunit G13 or its effector Arhgef1 caused an intestine-specific loss of all types of CD8+ TCR{beta} and TCR{gamma}{delta} IEL. G13-deficient IEL exhibited restricted intraepithelial movement and impaired maturation. Induction of intestinal CD8{beta}+ Trm upon infection was intact in the absence of G13-signaling, but the cells had poor access to the villous niche and defective survival that could be rescued by increasing TGF{beta}+ or interleukin (IL)15. In vivo CRISPR/Cas9 screening identified GPR132 as a G13-coupled receptor that regulates CD8{beta}+ IEL homeostasis and migration to lysophosphatidylcholine. Mice bearing G13-deficient T cells suffered more severe colitis and increased colorectal tumor growth. The selective requirement for G13-signaling for IEL positioning and survival in the villous niche has implications for therapeutic intervention.

immunology↗

bioRxiv2023

Vhl deletion in Dmp1-expressing cells alters MEP metabolism and promotes stress erythropoiesis

In recent years, general hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) enzyme inhibitors have been developed for the treatment of anemia due to renal disease and osteoporosis. However, it remains a challenge to target the HIF signaling pathway without dysregulating the skeletal and hematopoietic system. Here, we examined the effects of Vhl deletion in bone by performing longitudinal analyses of VhlcKO mice at 3, 6, 10, and 24 weeks of age, where at 10 and 24 weeks of age, high bone mass and splenomegaly are present. Using flow cytometry, we observed increased frequency (%) of CD71loTER119hiFSClo orthochromatophilic erythroblasts and reticulocytes in 10- and 24-week-old VhlcKO bone marrow (BM), which correlated with elevated erythropoietin levels in the BM and increased number of red blood cells in circulation. The absolute numbers of myeloerythroid progenitors (MEPs) in the BM were significantly reduced at 24 weeks. Bulk RNA-Seq of the MEPs showed upregulation of Epas1 (Hif1a) and Efnb2 (Hif2a) in VhlcKO MEPs, consistent with a response to hypoxia, and genes involved in erythrocyte development, actin filament organization, and response to glucose. Additionally, histological analysis of VhlcKO spleens revealed red pulp hyperplasia and the presence of megakaryocytes, both of which are features of extramedullary hematopoiesis (EMH). EMH in the spleen was correlated with the presence of mature stress erythroid progenitors, suggesting that stress erythropoiesis is occurring to compensate for the BM microenvironmental irregularities. Our studies implicate that HIF-driven alterations in skeletal homeostasis can accelerate erythropoiesis. Key Points* Dysregulation of HIF signaling in Dmp1+ bone cells induces stress erythropoiesis. * Skeletal homeostasis modulates erythropoiesis.

physiology↗

bioRxiv2021

Deletion of Vhl in Dmp1-expressing cells causes microenvironmental impairment of B cell lymphopoiesis

The contributions of skeletal cells to the processes of B cell development in the bone marrow (BM) have not been completely described. The von-Hippel Lindau protein (VHL) plays a key role in cellular responses to hypoxia. Previous work showed that Dmp1-Cre;Vhl conditional knockout mice (VhlcKO), which delete Vhl in late osteoblasts and osteocytes, display dysregulated bone growth and reduction in B cells. Here, we investigated the mechanisms underlying the B cell defects using flow cytometry and high-resolution imaging. In the VhlcKO BM, B cell progenitors were increased in frequency and number, whereas Hardy Fractions B-F were decreased. VhlcKO Fractions B-C cells showed increased apoptosis and quiescence. Reciprocal BM chimeras confirmed a B cell-extrinsic source of the VhlcKO B cell defects. In support of this, VhlcKO BM serum contained reduced CXCL12 and elevated EPO levels. Staining of VhlcKO B cells with an intracellular hypoxic marker indicated the natural existence of distinct B cell microenvironments that differ in local oxygen tensions. Additionally, intravital and ex vivo imaging revealed VhlcKO BM blood vessels with increased diameter, frequency, volume, and a diminished blood-BM barrier. Our studies identify novel mechanisms linking altered bone homeostasis with drastic BM microenvironmental changes that dysregulate B cell development.

immunology↗