Calcium Signaling in Immune Cells

Dear Colleagues,

Calcium (Ca²⁺) acts as a second messenger in many cell types, including immune cells. In the immune system, Ca²⁺ signals play a crucial role in their differentiation and maturation, phagocytosis, cytokine and chemokine secretion, enzyme production, migration, and antigen presentation. Interestingly, the duration and the amplitude of Ca²⁺ signals modulate each function differently. For instance, the long duration of calcium signal is associated with lymphocyte proliferation, cytokine or chemokine production; the differentiation of T cells; and anergy, while the short duration of Ca²⁺ signal transduction is related to the motility and degranulation of T cells. Moreover, IP3-mediated Ca²⁺ release from the endoplasmic reticulum (ER) generates repetitive [Ca²⁺]i oscillations that control c-fos gene expression in T lymphocytes. Repetitive or prolonged changes in intracellular Ca²⁺ are also required for the calcineurin-mediated dephosphorylation of the nuclear factor of an activated T cell (NFAT). The dysfunction of Ca²⁺-calcineurin-NFAT1 in autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, could be attenuated by calcineurin inhibitors, cyclosporine, and tacrolimus. NFAT activation depends on store-operated calcium entry (SOCE), a phenomenon mediated by the direct interaction between the plasma membrane channel Orai1 and the unique ER Ca²⁺ sensor stromal interaction molecule (STIM). Molecular and genetic approaches have demonstrated that components of the SOCE signaling pathway are crucial for the function of lymphocytes.

Similar to other immune cells, the prevalent calcium entry into innate immune cells is induced by cell-surface receptors that stimulate store-operated calcium entry through calcium-release-activated calcium channels. For this reason, the pharmacological modulation of calcium channels in innate cells has been suggested as a new therapeutic approach to various inflammatory and allergic diseases.

Furthermore, the executive functions of microglia, the resident immune cells of the CNS, are coupled to intracellular Ca²⁺ signaling. Microglia show spontaneous Ca²⁺ transients and express functional receptors directly coupled to changes in the intracellular free Ca²⁺ concentration. Interestingly, microglia share some of these properties with other immune cells, including monocytes invading the brain under pathological conditions such as brain ischemia.

In this Special Issue, we would like to discuss outstanding questions and probable future directions of the field. The question of how individual immune cells use different sources of Ca²⁺ influx during their lifespan should provide useful insights and will be the focus of this issue.

Prof. Dr. Agnese Secondo
Prof. Dr. Stefania Loffredo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• calcium signaling
• neurodegeneration
• immunodeficiencies
• cytokine
• microglia
• immune cells
• SOCE
• intracellular mediators
• angiogenesis
• organellar calcium