Innate Immune Activation Is a Strong Suppressor of CCL22 and Impedes Regulatory T Cell-Dendritic Cell Interaction.

The chemokine CCL22 is constitutively expressed at high levels in lymphoid organs, where it controls immunity by promoting contacts between dendritic cells (DC) and regulatory T cells (Treg). However, its regulation and impact in the context of pattern recognition receptor (PRR) stimulation and microbial infection are unknown. Here we show that CCL22 levels in lymphoid organs of mice were strongly suppressed upon stimulation with TLR agonists.

Constitutive Expression of CCL22 Is Mediated by T Cell-Derived GM-CSF.

CCL22 is a key mediator of leukocyte trafficking in inflammatory immune responses, allergy, and cancer. It acts by attracting regulatory T cells and Th2 cells via their receptor CCR type 4 (CCR4). Beyond its role in inflammation, CCL22 is constitutively expressed at high levels in lymphoid organs during homeostasis, where it controls immunity by recruiting regulatory T cells to dendritic cells (DCs).

CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes.

Chemokines have crucial roles in organ development and orchestration of leukocyte migration. The chemokine CCL22 is expressed constitutively at high levels in the lymph node, but the functional significance of this expression is so far unknown. Studying a newly established CCL22-deficient mouse, we demonstrate that CCL22 expression by dendritic cells (DCs) promotes the formation of cell-cell contacts and interaction with regulatory T cells (T reg) through their CCR4 receptor.

Suppression of intratumoral CCL22 by type i interferon inhibits migration of regulatory T cells and blocks cancer progression.

The chemokine CCL22 is abundantly expressed in many types of cancer and is instrumental for intratumoral recruitment of regulatory T cells (Treg), an important subset of immunosuppressive and tumor-promoting lymphocytes. In this study, we offer evidence for a generalized strategy to blunt Treg activity that can limit immune escape and promote tumor rejection. Activation of innate immunity with Toll-like receptor (TLR) or RIG-I-like receptor (RLR) ligands prevented accumulation of Treg in tumors by blocking their immigration.

Learning the facts in medical school is not enough: which factors predict successful application of procedural knowledge in a laboratory setting?

Background: Medical knowledge encompasses both conceptual (facts or "what" information) and procedural knowledge ("how" and "why" information). Conceptual knowledge is known to be an essential prerequisite for clinical problem solving. Primarily, medical students learn from textbooks and often struggle with the process of applying their conceptual knowledge to clinical problems.

In breast cancer, a high ratio of tumour-infiltrating intraepithelial CD8+ to FoxP3+ cells is characteristic for the medullary subtype.

Aims: Medullary breast cancer (MBC) is a biologically distinct subtype of breast cancer characterized by prominent lymphocytic infiltrates and a favourable clinical outcome. Tumour-infiltrating CD8+ effector T cells may contribute to the good prognosis of this type of cancer; however, certain subtypes of lymphocyte, such as FoxP3+ regulatory T cells (Tregs), can also suppress antitumour immunity.

Methods And Results: We determined tumour infiltration by FoxP3+, CCL22+ and CD8+ cells in paraffin-embedded sections of MBC, and, as a reference, in samples of grade 3 ductal, lobular and mucinous breast cancer.