SOJ Immunology

3

Authors: Yalcin AD, Suer K and Yalcin AN

Omalizumab, a humanized mAb that binds to the CH3 domain, near the binding site for the high-affinity type-I IgE Fc receptors of human IgE, can neutralize free IgE and inhibit the IgE allergic pathway without sensitizing mast cell and basophils. The clinical experience during the patient follow-up of an omalizumab treated severe persistent allergic asthma patient with complicated viral infection is introduced. A female patient (aged 58) with severe persistent allergic asthma, on omalizumab therapy had laryngeal oedema during a complicated common cold infection with bacterial sinusitis after omalizumab injection. Systemic steroids, ketotifen fumarate, antibiotic and antihistamines (desloratadine) were given. We did not stop omalizumab therapy. To our knowledge, this is the first time an association between omalizumab use and laryngeal oedema has been documented. In fact we do not know the exact mechanism behind this relationship. In conclusion we do not suggest Omalizumab during the first five days of complicated viral infections such as common cold and bacterial sinus infections.

6

Authors: Gabriela Mellado-Sanchez, Hector Vivanco-Cid, and Adriana Sumoza-Toledo

Dendritic Cells (DCs) are highly potent Antigen-Presenting Cells (APCs) that have a key role in mediating tolerance or immunity to self and non-self antigens. In their immature stage DCs are highly phagocytic and undergo a maturation process after taking up an antigen. DC maturation is characterized by activation of mechanisms of antigen presentation, increased expression of Major Histocompatibility Complex (MHC) class II and co-stimulatory molecules in the plasma membrane, and secretion of cytokines and chemokines. Despite the fact that the role of calcium (Ca2+) in DC function has been clearly established, regulation of Ca2+ signals in these cells is not well known. However, recently it has been demonstrated that functional capacitative Ca2+ release-activated Ca2+ (CRAC), Transient Receptor Potential Melastatin-2(TRPM2) and TRP Vanilloid- 1 (TRPV1) channels are critical for mouse DC maturation and migration. Also, Ryanodine Receptor-1 (RyR1) signaling activated by L-type Ca2+ channel CaV1.2 cause rapid MHC-II expression in the plasma membrane of DCs. The understanding of the regulation of Ca2+ signals in DCs is essential, to potentially modulate DC functions in disease processes. Therefore, in this review, we discuss recent studies on the expression and roles of Ca2+ channels in DC biology and function.

8

Authors: Houda Khatif and Ingo Drexler

Autophagy is a catabolic mechanism developed in eukaryotes in order to maintain cellular homeostasis and development. It is also an essential constituent of the immune system since it is involved in the MHC class I and II antigen generation and exerts an antiviral effect. However many viruses are either able to inhibit or induce autophagy to avoid their own elimination or to favor their replication by interacting with different complexes of the autophagy pathway. This review summarizes the molecular mechanisms of autophagy and its importance in immunity. It describes the different strategies that viruses have adopted to hijack this process.

2

Authors: Young I. Choi

When I was asked to write 2-page editorial for Symbiosis Online Journal Immunology, I contemplated the meaning of symbiosis in immunology. The first thing that came up in my mind was the question how I can connect the symbiosis to drug development. When I started postdoctoral work in the laboratory of Dr. Reinherz at Dana-Farber Cancer Institute, Harvard Medical School, I was fascinated with the beautiful tissue organization of thymus. Thymus is constituted with several irregular roundshape medulla surrounded by outer cortex. The outer cortex is densely packed with CD4+ CD8+ double positive immature thymocytes but the inner medulla is filled with CD4+ or CD8+ single positive mature T cells. Thymic epithelial cells secrete several chemokines such as CXCL12, CCL19 and CCL21. These chemokines control thymocyte migration for the clear separation of developing thymocytes into different thymic compartment. My first question was why each animal has different shape and distribution of medulla. If thymic epithelial cell development is the first step for the construction of thymic architecture, I guessed that all the organisms should have a similar pattern in medulla distribution. The irregularity of medulla distribution suggested that thymic epithelial development is not dependent on epithelial cell alone but on the interaction with other cells such as developing thymocytes. When T cell development was induced with anti CD3ε antibody injection into the TCRβ+ Rag2- /- mice where thymus has only cortex and T cell development was blocked at CD4+ CD8+ double positive stage, T cell development was resumed temporarily and the medulla developed again promptly [1]. This result suggested that the interaction between epithelium and lymphocyte affects the development of both sides

3

Authors: Ian Adcock and Yassine Amrani

Accumulating evidence now shows that low level of vitamin D is associated with the development and/or aggravation of a number of lung diseases in both adults and children [1-3]. Clinically, low levels of vitamin D refers to hormone deficiency which is defined by a serum level <20ng/mL [4]. Vitamin D insufficiency, typically defined by levels ranging from 20-29ng/ mL, has also been regarded as clinically important particularly in children [5]. Despite numerous reports associating vitamin D levels to allergic disorders, the cellular and molecular pathways explaining the protective role of vitamin D in lung diseases have not been fully investigated. The purpose of this short review is to describe the current evidence describing the importance of vitamin D in modulating patient’s response to corticosteroid therapy.

7

Authors: Rakel Carpintero, Karim J. Brandt, Lyssia Gruaz and Danielle Burger

Deregulation of the production of IL-1β and its natural inhibitor, the secreted form of IL-1 receptor antagonist (sIL-1Ra), plays an important role in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. Relevant to the latter conditions direct cellular contact with stimulated T cells potently triggers cytokine production in human monocytes. Identification of signal transduction pathways specific to pathogenic induction of cytokines may lead to new therapeutic approaches. Two different stimuli were compared to investigate the implication of MEK1 and MEK2 in the control of IL-1β and sIL-1Ra production by human monocytes: (i) soluble extracts of plasma membranes from stimulated T cells (CEsHUT), mimicking cellular contact with T cells, i.e., chronic/sterile inflammatory conditions; and (ii) LPS that is relevant to infectious inflammation. The ATP-noncompetitive MEK1/2 (U0126) and MEK1 (PD98059) specific inhibitors diminished the expression (protein and mRNA) of IL-1β in CEsHUT-activated monocytes. In contrast, only the concomitant inhibition of MEK1 and MEK2 inhibited IL-1β production in LPS-activated monocytes, whereas the inhibition of MEK1 only did not affect IL-1β production. In CEsHUT- and LPS-activated monocytes, MEK1 inhibition slightly affected sIL-1Ra production that was significantly inhibited by U0126. These results suggest that MEK1 and MEK2 are differentially involved in the regulation of the IL-1 system upon chronic/sterile and infectious inflammatory conditions. MEK1 which is dispensable to IL-1β production in LPS-activated monocytes represents a potential therapeutic target whose inhibition could participate in the restoration of IL-1β/sIL-1Ra balance in chronic/sterile inflammation without affecting regular responses to pathogens.