The Role of Different Circulating T Follicular Helper Cell Markers in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic incurable inflammatory autoimmune disease. T follicular helper (Tfh) cells expressing different markers play critical roles in the development of RA. However, their specific mechanisms of action and association with RA clinical parameters are not clear.

Interleukin-29 and interleukin-28A induce migration of neutrophils in rheumatoid arthritis.

Objectives: Type III Interferons, interleukin (IL)-29 and IL-28A, have been implicated in the inflammatory response of rheumatoid arthritis (RA). Increasing evidence suggests an important role of neutrophils in the pathogenesis of RA. However, the underlying mechanism remains unclear.

Interleukin-29 regulates T follicular helper cells by repressing BCL6 in rheumatoid arthritis patients.

Introduction: We aimed to investigate whether Interleukin-29 (IL-29) directly affects T follicular helper (Tfh) cell frequency in rheumatoid arthritis (RA), which are both related to RA-specific antibody responses.

Methods: Here, we explored the effect of IL-29 on Tfh cell production in RA patients using a combination of enzyme-linked immunosorbent assay (ELISA), flow cytometry (FCM), CD4 T cell culture, western blotting, and reverse transcription-polymerase chain reaction (RT-PCR).

Results: We reported that serum IL-29 levels, peripheral blood CD4CXCR5 Tfh cell frequency, CD4CXCR5CD40L Tfh cell frequency, and IL-28 receptor (IL-28Rα) and IL-10 receptor (IL-10R2) levels in peripheral blood Tfh cells were higher in RA patients than in healthy controls (HCs).

RhoGDI2 positively regulates the Rho GTPases activation in response to the β2 outside-in signaling in T cells adhesion and migration on ICAM-1.

Cytoskeletal reorganization driven by Rho GTPases plays a crucial role in the migration of T cells, which are key regulators of immunity. The molecular mechanisms that control actin cytoskeleton remodeling during T cell movement have only partially been clarified as the function of many modulators has not been evaluated in these cells. Here, we report a new function of RhoGDI2 by showing that this protein positively regulates Rho GTPase activation during T cell adhesion and migration.

Effective serum level of etanercept biosimilar and effect of antidrug antibodies on drug levels and clinical efficacy in Chinese patients with ankylosing spondylitis.

Objectives: To investigate the effective serum level of etanercept biosimilar in Chinese patients with ankylosing spondylitis (AS) who achieve AS Disease Activity Score-C-reactive protein (ASDAS-CRP) < 2.1, and the effect of antidrug antibodies on drug levels and clinical efficacy.

Methods: Our study enrolled 60 patients with AS who were treated with etanercept biosimilar.

Lipid raft‑associated β‑adducin participates in neutrophil migration.

Previous studies have demonstrated that lipid rafts and β‑adducin serve an important role in leukocyte rolling. In the present study the migratory ability and behavior of neutrophils was demonstrated to rely on the integrity of the lipid raft structure. β‑adducin was demonstrated to have a critical role in neutrophil migration.

Elevated Serum Levels of Interleukin-29 Are Associated with Disease Activity in Rheumatoid Arthritis Patients with Anti-Cyclic Citrullinated Peptide Antibodies.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that may lead to progressive joint destruction. The anti-cyclic citrullinated peptide (anti-CCP) antibody is an essential marker for the diagnosis of RA and has a crucial role in the bone destruction in RA. Recent studies have shown that interleukin (IL)-29, a vital member of type III interferon (IFN) family, could enhance proinflammatory cytokine production and might be involved in the joint destruction in RA.

Lipid raft-associated β-adducin is required for PSGL-1-mediated neutrophil rolling on P-selectin.

Lipid rafts, a liquid-ordered plasma membrane microdomain, are related to cell-surface receptor function. PSGL-1, a major surface receptor protein for leukocyte, also acts as a signaling receptor in leukocyte rolling. To investigate the role of lipid raft in PSGL-1 signaling in human neutrophils, we quantitatively analyzed lipid raft proteome of human promyelocytic leukemia cell line HL-60 cells and identified a lipid raft-associated protein β-adducin.

Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.

P-selectin glycoprotein ligand-1 (PSGL-1) and integrins are adhesion molecules that play critical roles in host defense and innate immunity. PSGL-1 mediates leukocyte rolling and primes leukocytes for integrin-mediated adhesion. However, the mechanism that PSGL-1 as a rolling receptor in regulating integrin activation has not been well characterized.

PI3K is involved in β1 integrin clustering by PSGL-1 and promotes β1 integrin-mediated Jurkat cell adhesion to fibronectin.

P-selectin glycoprotein ligand-1 (PSGL-1) is involved in the initial step of lymphocyte homing by interacting with P- or E-selectins expressed on activated endothelium cells. Besides, it also functions as a receptor to induce signals that increase integrin affinity to ligands and mediate cell adhesion to endothelium. Integrin is required for the second step of lymphocyte homing, whose activation has been reported tightly regulated by inside-out signals triggered by chemokines or the shear-stress generated during lymphocyte rolling on endothelium.

p85-RhoGDI2, a novel complex, is required for PSGL-1-induced β1 integrin-mediated lymphocyte adhesion to VCAM-1.

P-selectin glycoprotein ligand-1 and β1 integrin play essential roles in T cell trafficking during inflammation. E-selectin and vascular cell adhesion molecule-1 are their ligands expressed on inflammation-activated endothelium. During the tethering and rolling of lymphocytes on endothelium, P-selectin glycoprotein ligand-1 binds E-selectin and induces signals.

PI3K is involved in L-selectin- and PSGL-1-mediated neutrophil rolling on E-selectin via F-actin redistribution and assembly.

L-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) are adhesion molecules that play critical roles in neutrophil rolling during inflammation and lymphocyte homing. On the other hand they also function as signaling receptors to induce cytoskeleton changes. The present study is to investigate the signaling kinases responsible for the F-actin changes mediated by L-selectin and PSGL-1 during neutrophil rolling on E-selectin.