Heterogeneous IL-9 Production by Circulating Skin-Tropic and Extracutaneous Memory T Cells in Atopic Dermatitis Patients.

Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA and extracutaneous/systemic CLA memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB).

Oncogenic Gαq activates RhoJ through PDZ-RhoGEF.

Oncogenic Gα causes uveal melanoma via non-canonical signaling pathways. This constitutively active mutant GTPase is also found in cutaneous melanoma, lung adenocarcinoma, and seminoma, as well as in benign vascular tumors, such as congenital hemangiomas. We recently described that PDZ-RhoGEF (also known as ARHGEF11), a canonical Gα effector, is enabled by Gα Q227L to activate CdcIn addition, and we demonstrated that constitutively active Gα interacts with the PDZ-RhoGEF DH-PH catalytic module, but does not affect its binding to RhoA or Cdc.

CaSR links endocytic and secretory pathways via MADD, a Rab11A effector that activates Rab27B.

Calcium sensing receptor (CaSR), a class C GPCR, regulates essential secretory pathways, involving communication between endocytic and secretory Rab GTPases, via still to be fully defined molecular mechanisms. To address how communication between endocytic and secretory vesicles occurs, we hypothesized that CaSR activates endocytic Rab11A-dependent effector pathways acting upstream of Rab27B-regulated secretion. We found that Rab11A is critical to promote Rab27B-dependent secretion of chemotactic and inflammatory factors, including IL-8, CCL2/MCP-1, and IL1-β, in response to CaSR stimulation.

Guanine nucleotide exchange factors for Rho GTPases (RhoGEFs) as oncogenic effectors and strategic therapeutic targets in metastatic cancer.

Metastatic cancer cells dynamically adjust their shape to adhere, invade, migrate, and expand to generate secondary tumors. Inherent to these processes is the constant assembly and disassembly of cytoskeletal supramolecular structures. The subcellular places where cytoskeletal polymers are built and reorganized are defined by the activation of Rho GTPases.

Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients.

Background: The role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized.

Methods: The response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients.