Helper T Cells in Idiopathic Membranous Nephropathy

Abstract

Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the immune system produces an antibody response to its own antigens due to impaired immune tolerance. Although antibodies are derived from plasma cells differentiated by B cells, the T-B cells also contribute a lot to the immune system. In particular, the subsets of helper T (Th) cells, including the dominant subsets such as Th2, Th17, and follicular helper T (Tfh) cells and the inferior subsets such as regulatory T (Treg) cells, shape the immune imbalance of IMN and promote the incidence and development of autoimmune responses. After reviewing the physiological knowledge of various subpopulations of Th cells and combining the existing studies on Th cells in IMN, the role model of Th cells in IMN was explained in this review. Finally, the existing clinical treatment regimens for IMN were reviewed, and the importance of the therapy for Th cells was highlighted.

New-Onset and Relapsed Membranous Nephropathy post SARS-CoV-2 and COVID-19 Vaccination

“…T helper (Th) 17 cells generated interleukin (IL)-17A, IL-17F, IL-22, and granulocyte-macrophage colony-stimulating factor, inducing the aggregation of inflammatory cells, such as neutrophils [ 43 ]. IL-4 produced by Th2 cells and IL-21 produced by follicular T helper (Tfh) cells contributed to B lymphocyte survival and proliferation as well as generated higher affinity to the IgG4 antibody [ 44 ]. Moreover, IL-4, IL-13, and IL-10 could promote the conversion of antibody category to IgG4 [ 44 ].…”

“…IL-4 produced by Th2 cells and IL-21 produced by follicular T helper (Tfh) cells contributed to B lymphocyte survival and proliferation as well as generated higher affinity to the IgG4 antibody [ 44 ]. Moreover, IL-4, IL-13, and IL-10 could promote the conversion of antibody category to IgG4 [ 44 ]. In addition, decreased levels of Th1 cells and regulatory T (Treg) cells secondary to SARS-CoV-2 infection destroyed immune tolerance [ 45 ].…”

Case Report: Atypical Manifestations Associated With FOXP3 Mutations. The “Fil Rouge” of Treg Between IPEX Features and Other Clinical Entities?

“…The variety of kidney alteration in IPEX could be explained by the role of FOXP3 on regulatory T cells. Tregs have, in fact, functional plasticity in response to different immune and genetic environment ( 24 ), and the dysregulation of Tregs could produce two major effects: one is the stimulation of IgG4 autoantibodies versus renal-specific antigens (PLA2R1 and THSD7A are the major) in membranous glomerulopathy, while the second potential effect of Tregs dysfunction is the increase of the release of cytokines by effector T cells that affect podocyte function (with the development of minimal change disease) ( 25 ). In IPEX syndrome, the pathogenesis of membranous glomerulopathy is consistent, with an imbalance between Treg and Th17 ( 26 ) that is due to a significant reduction of Tregs and FOXP3 expression ( 27 ) in the presence of Th17 stable levels.…”

Role of Histone Deacetylases in T-Cell Development and Function

“…T-cells are divided into subsets according to their function and expression of certain surface antigens. Helper T-cells (Th cells) expressing CD4 antigen are components of the adaptive immune system [ 36 ]. They play a role as “helpers” for other immune cells to release cytokines, which act as mediators to target cells [ 37 ].…”