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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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TGF - β Signaling Pathway01:16

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Intracellular Signaling Affects Focal Adhesions01:17

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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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Smooth Muscle Contraction01:25

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Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
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Inflammatory Response01:28

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An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Related Experiment Video

Updated: Jun 14, 2025

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

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A CD4+ T cell-intrinsic complement C5aR2-prostacyclin-IL-1R2 axis orchestrates Th1 cell contraction.

Jubayer Rahman1, Jack A Bibby1, Parul Singh1

  • 1Complement and Inflammation Research Section, NHLBI, NIH, Bethesda, MD 20892, USA.

Immunity
|May 31, 2025
PubMed
Summary

Complement C5 triggers a pathway that reduces T helper 1 (Th1) cell activity by shifting lipid mediator production. This mechanism, when disrupted, causes persistent Th1 inflammation in autoimmune diseases.

Keywords:
C5aR2CAPSCrohn’s diseaseIL-1βTh1 cell responsescomplementcomplosomecryopyrin-associated periodic fever syndromeprostacyclinprostaglandinrheumatoid arthritis

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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
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Area of Science:

  • Immunology
  • Molecular Biology
  • Inflammation Research

Background:

  • T helper 1 (Th1) cell initiation is understood, but their contraction pathways are not.
  • Persistent Th1 cell activity contributes to various inflammatory conditions.

Purpose of the Study:

  • To elucidate the molecular mechanisms controlling Th1 cell contraction.
  • To identify potential therapeutic targets for inflammatory diseases characterized by excessive Th1 cell activity.

Main Methods:

  • Investigated a CD4+ T cell-autonomous pathway involving complement C5.
  • Analyzed lipid mediator production (PGE2 and PGI2) and receptor signaling (C5aR2, PGI2 receptor).
  • Examined the role of IL-1 receptor type 2 (IL-1R2) in sequestering IL-1β.

Main Results:

  • Complement C5 activation of C5aR2 shifts lipid mediator production from PGE2 to PGI2.
  • This shift promotes autocrine PGI2 signaling, leading to IL-1R2 expression and IL-1β sequestration.
  • Disruption of the C5aR2-PGI2-R axis is linked to persistent Th1 activity in CAPS, Crohn's disease, and rheumatoid arthritis.
  • Selective PGE2 synthase inhibition reversed hyperactive Th1 cell phenotype in vitro.

Conclusions:

  • Complement C5 is a critical regulator of prostanoid metabolism influencing Th1 cell contraction.
  • The C5aR2-PGI2-R axis represents an intrinsic checkpoint for terminating Th1 cell effector responses.
  • This pathway is a potential therapeutic target for inflammatory disorders.