Pathophysiological Roles of Cytokine-Chemokine Immune Network

摘要

Cytokines are small proteins or glycoproteins, and chemokines form a group of smaller cytokines with chemotactic properties that are produced by a variety of cells. Cytokines and chemokines exert crucial roles in the development, homeostasis, activation, differentiation, regulation, and functions of innate and adaptive immunity. Excessive and/or inappropriate production and actions of cytokines and chemokines are involved in the pathogenesis of infection, inflammation, allergy, autoimmune diseases, and immune-related diseases, such as diabetes, atherosclerosis, rheumatic arthritis, and cancer. Understanding the underlying mechanisms by which cytokines and chemokines exert their functions will lead to development of therapeutics for immune-related diseases. In this special issue, the articles and reviews discuss recent findings that highlight the pathophysiological role of cytokine and chemokines.Effector and memory T cells are phenotypically and functionally heterogeneous. Upon antigenic stimulation, nave CD4~(+) T cells become effector Th1, Th2, or Th17 cells or regulatory T cells (Tregs). Effector and regulatory T cell subsets are generated in the presence of specific cytokines such as IL-12 and TGF- , respectively. Transcription factors initiate and stabilize commitment toward the Th1 or Th2 lineage. T-bet (the T-box protein expressed in T cells) is the master regulator of Th1 differentiation [1]. A review article by S. Oh and E. S. Hwang summarizes the current state of knowledge regarding the molecular mechanisms that underlie the multiple roles played by T-bet in T helper cell development and fine-modulation of IL-2 production in Th1 cells. Interestingly, IFN- stimulation of dendritic cells (DCs) might have an equally important role in generating different effector T cells [2]. In this special issue, A. Visperas et al. describe several cytokines that are able to influence the generation of effector T cells by directly affecting T cells as well as targeting non-T cells. Inflammatory cytokine signaling also plays an important role in the pathogenic conversion of natural Tregs. The article by R. Takahashi and A. Yoshimura is a review in which the possibility is proposed that suppressor of cytokine signaling 1 (SOCS1) may protect Tregs from harmful effects of inflammatory cytokines, and SOCS1 upregulation maintains Treg functions. SOCS1 may be important in the pathogenesis of systemic lupus erythematosus through Treg plasticity, because SOCS1-deficient T cells induce lupus-like autoimmunity [3].