IL-4 is known to be the quintessential regulatory cytokine, playing a role in a vast number of immune and non-immune functions. This cytokine is commonly secreted by type 2 helper T (TH2) cells and follicular helper T (TFH) cells after antigenic sensitization. TH2 cells have been classically thought to be the major contributor to B-cell help as a source of IL-4 responsible for class-switch recombination to IgG1 in mice (IgG4 in humans) and to IgE in mice and humans. Recent in vivo observations have shown that IgE and IgG1 antibody responses are mainly controlled by IL-4-secreting TFH cells but not by classical TH2 cells. IL-4 is distinctively regulated in these two T-cell subsets by the GATA-3-mediated HS2 enhancer in TH2 cells and the Notch-mediated conserved non-coding sequence 2 (CNS-2) enhancer in TFH cells. Moreover, the IL-4 derived from TFH cells has an essential role in germinal center (GC) formation in the secondary lymphoid organs during humoral immune responses.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/intimm/dxab080 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Boosting human immunology: harnessing the potential of immune organoids.
EMBO Mol Med
January 2025
Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Studying the human immune system in vivo is challenging and often not possible. Therefore, most human immunology studies have been predominantly confined to peripheral blood analyses, which by themselves have inherent limitations, as many immune reactions take place within tissues. For example, potent antibody responses that contribute to fighting infections and provide protection following vaccination require cellular interactions between B cells and T cells in specialized micro-anatomical structures called germinal centers, which are found in secondary lymphoid organs such as spleen, lymph nodes, and tonsils.
View Article and Find Full Text PDFUnlabelled: Dendritic cells (DCs) are key regulators of adaptive immunity, guiding T helper (Th) cell differentiation through antigen presentation, co-stimulation, and cytokine production. However, in steady-state conditions, certain DC subsets, such as Langerhans cells (LCs), induce T follicular helper (Tfh) cells and B cell responses without inflammatory stimuli. Using multiple mouse models and systems, we investigated the mechanisms underlying steady-state LC-induced adaptive immune responses.
View Article and Find Full Text PDFInitiation of primary T cell-B cell interactions and extrafollicular antibody responses in an organized microphysiological model of the human lymph node.
bioRxiv
January 2025
Department of Chemistry, 409 McCormick Road, University of Virginia, Charlottesville, VA 22904.
Antibody production is central to protection against new pathogens and cancers, as well as to certain forms of autoimmunity. Antibodies often originate in the lymph node (LN), specifically at the extrafollicular border of B cell follicles, where T and B lymphocytes physically interact to drive B cell maturation into antibody-secreting plasmablasts. In vitro models of this process are sorely needed to predict aspects of the human immune response.
View Article and Find Full Text PDFT Cell-Specific Inactivation of the PI3K p110α Catalytic Subunit: Effect in T Cell Differentiation and Antigen-Specific Responses.
Int J Mol Sci
January 2025
Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220 Madrid, Spain.
Class IA PI3K p110δ and p110α subunits participate in TCR and costimulatory receptor signals involved in T cell-mediated immunity, but the role of p110α is not completely understood. Here, we analyzed a mouse model of the Cre-dependent functional inactivation of p110α (kinase dead) in T lymphocytes (p110αKD-T, KD). KD mice showed increased cellularity in thymus and spleen and altered T cell differentiation with increased number of CD4CD8 DP thymocytes, enhanced proportion of CD4 SP lymphocytes linked to altered apoptosis, lower Treg cells, and increased AKT and ERK phosphorylation in activated thymocytes.
View Article and Find Full Text PDFThe Inhibitory Effects of Alpha 1 Antitrypsin on Endosomal TLR Signaling Pathways.
Biomolecules
January 2025
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Endosomal toll-like receptors (TLRs) TLR7, TLR8, and TLR9 play an important role in systemic lupus erythematosus (SLE) pathogenesis. The proteolytic processing of these receptors in the endolysosome is required for signaling in response to DNA and single-stranded RNA, respectively. Targeting this proteolytic processing may represent a novel strategy to inhibit TLR-mediated pathogenesis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!