Copyright@ Jea-Hyun Baek | Biomed J Sci & Tech Res| BJSTR. MS.ID.003458. 15062 Mini Review ISSN: 2574 -1241 Interleukin-34: Regulator of T Lymphocytes in Rheumatoid Arthritis Jea-Hyun Baek* Research and Development, Biogen Inc, US *Corresponding author: Jea-Hyun Baek, Biogen Inc., 225 Binney St, Cambridge, MA 02142, US DOI: 10.26717/BJSTR.2019.20.003458 Received: August 05, 2019 Published: August 12, 2019 Citation: Jea-Hyun Baek. Interleu- kin-34: Regulator of T Lymphocytes in Rheumatoid Arthritis. Biomed J Sci & Tech Res 20(3)-2019. BJSTR. MS.ID.003458. ARTICLE INFO Abstract Interleukin-34 (IL-34) is a pleiotropic cytokine, which is implicated in various autoimmune diseases. Interestingly, clinical studies have found that IL-34 is markedly upregulated in the serum and synovium of patients with rheumatoid arthritis (RA), giving rise to a growing interest in understanding the role of IL-34 in RA. Although several studies demonstrated that IL-34 levels closely correlate with the disease severity, the function of circulating and synovial IL-34 in RA is still largely elusive. IL-34 was originally identified as a ligand of the colony-stimulating factor-1 receptor (CSF-1R), which is crucial for the survival, proliferation, and differentiation of mononuclear phagocytes (e.g. monocytes, macrophages [M] and dendritic cells [DC]). Of note, these IL-34-responsive cells are antigen-presenting cells, which bridge innate and adaptive immunity (e.g. through priming and instructing T lymphocytes). Thus, synovial IL-34 expression has been associated with the regulation of synovial M and linked to pathologic T-cell activation in RA. In this review, we discuss the current state of knowledge on the role of IL-34 in RA and, especially, focus on the impact of IL-34 on T lymphocyte activation in RA based on findings from translational and clinical studies. Abbreviations: CSF-1: Colony-Stimulating Factor-1; CSF-1R: CSF-1 Receptor; DC: Dendritic Cell(s); HLA: Human Leukocyte Antigen; IFN: Interferon; M: Macrophage(s); LITAF: lipopolysaccharide-Induced TNF factor LPS: lipopolysaccharide; PBMC: Peripheral Blood Mononuclear Cell(s); PTP-: Receptor-Type Tyrosine-Protein Phosphatase Zeta; RA: Rheumatoid Arthritis; Teff: Effector T Lymphocyte(s); TNF-: Tumor Necrosis Factor Alpha; Treg: Regulatory T Lymphocyte(s) Introduction Rheumatoid Arthritis (RA) is a common inflammatory autoimmune disease with complex etiologies, which primarily affects joints. RA is primarily caused by self-reactive immune responses and involves a variety of immune cells, including (1) innate immune cells (e.g. macrophages (M) and neutrophils), which are the first responders in inflammation; and (2) adaptive immune cells (e.g. B and T lymphocytes), which trigger highly effective secondary immune responses targeting specific antigens. M, neutrophils, and effector T lymphocytes (Teff) are prominent immune cells in the synovium of RA patients [1]. Interestingly, several alleles of human leukocyte antigen (HLA) class II histocompatibility antigen, DRB1 beta chain (encoded by HLA- DRB1) have been highly associated with increased incidence of RA and higher inflammatory activity in early RA [2-5], indicating that the interaction between antigen-presenting cells and T lymphocytes followed by an aberrant T-cell activation is a key mechanism in the pathogenesis of RA. Recently, the monocyte/M/dendritic cell (DC) cytokine IL- 34 has been suggested as a biomarker and therapeutic target in RA [6-8], supported by clinical studies demonstrating that IL-34 is robustly elevated in the serum, synovial fluid, and tissue in patients with RA [8-15]. However, while increasing evidence indicates that IL-34 plays an important role in the pathogenesis of RA, the precise mechanism underlying the increased levels of circulating and synovial IL-34 in RA [6], as well as the exact role of IL-34 in the pathophysiology of RA remains elusive. Although several functions