Modulation of the Interleukin-21 Pathway with Interleukin-4 Distinguishes Common Variable Immunodeficiency Patients with More Non-infectious Clinical Complications.

Purpose: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and clinical manifestations such as infections, autoimmunity, and malignancy. We sought to determine if responsiveness to interleukin-21 (IL-21), a key cytokine for B cell differentiation, correlates with distinct clinical phenotypes in CVID.

Methods: CVID subjects were recruited through the Canadian Primary Immunodeficiency Evaluative Survey registry.

Corrigendum: Semaphorin 4C: A Novel Component of B-Cell Polarization in Th2-Driven Immune Responses.

[This corrects the article on p. 558 in vol. 7, PMID: 28003812.

Peripherally Generated Foxp3 Regulatory T Cells Mediate the Immunomodulatory Effects of IVIg in Allergic Airways Disease.

IVIg is widely used as an immunomodulatory therapy. We have recently demonstrated that IVIg protects against airway hyperresponsiveness (AHR) and inflammation in mouse models of allergic airways disease (AAD), associated with induction of Foxp3 regulatory T cells (Treg). Using mice carrying a transgene under the control of the promoter (DEREG mice), we demonstrate in this study that IVIg generates a de novo population of peripheral Treg (pTreg) in the absence of endogenous Treg.

Semaphorin 4C: A Novel Component of B-Cell Polarization in Th2-Driven Immune Responses.

Background: Semaphorins are important molecules in embryonic development and multiple semaphorins have been identified as having key roles in immune regulation. To date, there is little known about Semaphorin 4C (Sema4C) in immune biology. We report for the first time that Sema4C is inducible in human and murine B-cells and may be important for normal B-cell development.

Semaphorin 4C Protects against Allergic Inflammation: Requirement of Regulatory CD138+ Plasma Cells.

The regulatory properties of B cells have been studied in autoimmune diseases; however, their role in allergic diseases is poorly understood. We demonstrate that Semaphorin 4C (Sema4C), an axonal guidance molecule, plays a crucial role in B cell regulatory function. Mice deficient in Sema4C exhibited increased airway inflammation after allergen exposure, with massive eosinophilic lung infiltrates and increased Th2 cytokines.

CC and CXC chemokines induce airway smooth muscle proliferation and survival.

The increase in airway smooth muscle (ASM) mass is a major structural change in asthma. This increase has been attributed to ASM cell (ASMC) hyperplasia and hypertrophy. The distance between ASMC and the epithelium is reduced, suggesting migration of smooth muscle cells toward the epithelium.