Targeting Inflammatory T Cells in Multiple Sclerosis: Current Therapies and Future Challenges

Multiple Sclerosis (MS) is an autoimmune inflammatory disorder of the Central Nervous System (CNS), affecting more than one million people worldwide. The pathogenesis of MS involves several genetic and environmental factors, which ultimately lead to the activation of autoreactive T cells in the periphery, their migration into the CNS, where they trigger an acute inflammatory response, thus mediating primary demyelination and axonal damage. Most information on MS derives from studies in animal models of experimental autoimmune encephalomyelitis (EAE), which exhibit many similarities to the pathology of MS. Two distinct subsets of autoreactive T cells have been primarily involved in the pathogenesis of both EAE and MS: the interferon (IFN)-γ producing CD4+ T helper (Th) 1 and interleukin (IL)-17 producing Th17 cells. The activity of these cells is controlled by specific regulatory T cells (Treg), which by secreting antiinflammatory cytokines such as IL-4, IL-10 and tumour growth factor (TGF)-β efficiently inhibit Th1 and Th17 cells. In this review, we summarize current knowledge on the role and function of pro-inflammatory and Treg subsets in MS. We also discuss the action of current and novel therapies aimed to dampen inflammatory T cells

Editorial: Membrane lipids in T cell functions

Plasma membrane lipids play essential roles in regulating T cell signaling, differentiation, and effector functions. The major lipid species in the plasma membrane are glycerophospholipids, sphingolipids, and sterol lipids. TCR and costimulatory molecules lead to profound changes in the composition, distribution, and dynamic of plasma membrane lipids. For instance, cholesterol, sphingomyelin, and saturated phosphocholine are enriched at the contact zone between T cells and antigen-presenting cells during peptide/MHC complexes recognition, where they constitute a platform of lipid domains essential for optimal T cell signaling. Glycerophospholipid provide docking sites for binding pivotal signaling proteins as well as for their conformation, portioning, and mobility. Finally, plasma membrane lipids also act as second messengers with important immune-regulatory functions. This Research Topic contains seven articles that review the current understanding of the mechanisms and molecules involved in the metabolism and function of membrane lipids and how differences in their content may affect T cell functional properties

Enforcing Architectural Styles in Presence of Unexpected Distributed Reconfigurations

Architectural Design Rewriting (ADR, for short) is a rule-based formal framework for modelling the evolution of architectures of distributed systems. Rules allow ADR graphs to be refined. After equipping ADR with a simple logic, we equip rules with pre- and post-conditions; the former constraints the applicability of the rules while the later specifies properties of the resulting graphs. We give an algorithm to compute the weakest pre-condition out of a rule and its post-condition. On top of this algorithm, we design a simple methodology that allows us to select which rules can be applied at the architectural level to reconfigure a system so to regain its architectural style when it becomes compromised by unexpected run-time reconfigurations.Comment: In Proceedings ICE 2012, arXiv:1212.345

Towards Nominal Formal Languages

We introduce formal languages over infinite alphabets where words may contain binders. We define the notions of nominal language, nominal monoid, and nominal regular expressions. Moreover, we extend history-dependent automata (HD-automata) by adding stack, and study the recognisability of nominal languages

Heuristic Methods for Security Protocols

Model checking is an automatic verification technique to verify hardware and software systems. However it suffers from state-space explosion problem. In this paper we address this problem in the context of cryptographic protocols by proposing a security property-dependent heuristic. The heuristic weights the state space by exploiting the security formulae; the weights may then be used to explore the state space when searching for attacks

Honesty by typing

We propose a type system for a calculus of contracting processes. Processes may stipulate contracts, and then either behave honestly, by keeping the promises made, or not. Type safety guarantees that a typeable process is honest - that is, the process abides by the contract it has stipulated in all possible contexts, even those containing dishonest adversaries

Style-Based architectural reconfigurations

We introduce Architectural Design Rewriting (ADR), an approach to the design of reconfigurable software architectures whose key features are: (i) rule-based approach (over graphs); (ii) hierarchical design; (iii) algebraic presentation; and (iv) inductively-defined reconfigurations. Architectures are modelled by graphs whose edges and nodes represent components and connection ports. Architectures are designed hierarchically by a set of edge replacement rules that fix the architectural style. Depending on their reading, productions allow: (i) top-down design by refinement, (ii) bottom-up typing of actual architectures, and (iii) well-formed composition of architectures. The key idea is to encode style proofs as terms and to exploit such information at run-time for guiding reconfigurations. The main advantages of ADR are that: (i) instead of reasoning on flat architectures, ADR specifications provide a convenient hierarchical structure, by exploiting the architectural classes introduced by the style, (ii) complex reconfiguration schemes can be defined inductively, and (iii) style-preservation is guaranteed