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The traditional view of the central nervous system (CNS) as an immune-privileged organ yielded a longstanding perception of such interactions—as seen for example in multiple sclerosis (MS) 1, 2—as intrinsically destructive. This notion is changing with the identification of several homeostatic functions attributable to beneficial T-cell/CNS interaction 3, for example in hippocampal-dependent learning 4 and stress response paradigms 5, and in models of neurodegeneration and CNS injury 6. Here we provide insights into the maintenance, and dynamics of the meningeal T-cell repertoire. We show that meningeal T-cell composition is coupled to the CNS-draining deep cervical lymph nodes (dCLNs), whose surgical removal interrupted the normal flow of meningeal T-cells and resulted in cognitive impairment.

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4+ T cells from wild-type mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell-derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4-producing CD4+ T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration.

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functional recovery following CNS injury; however, transfer of [CD4.sup.+] T cells from wild-type mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell-derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4-producing [CD4.sup.+] T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration.

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4 super( +) T cells from wild-type mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell-derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4-producing CD4 super( +) T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration.

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4^sup +^ T cells from wild-type mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell-derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4-producing CD4^sup +^ T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration.

Abstract Itch: its complex neurobiology, its exquisite evolutionary conservation, and even the undeniably euphoric sensation of the scratch it evokes, are all suggestive of a productive physiological function. Nevertheless, we still struggle to answer (or altogether overlook) the basic question of why we itch in the first place. Here, we propose a simple hypothesis: the purpose of itch sensation is to evoke scratching behavior, which in turn boosts protective immunity against the broad range of pathogenic challenges that enter at the skin. We propose that the key function of itch induced scratching is to physically disrupt the skin, serving as a “mechanical adjuvant” that amplifies and directs immune responses to the precise site of potential pathogen entry. As proof of principle, we show that the potent adjuvanticity of itch inducing Compound 48/80 is dependent on this agent’s ability to elicit scratching behavior. Footnotes * ↵* Former affiliation, based on affiliation at time of experimentation * author affiliations updated

We study the following question: suppose that A and ℬ are two algebras of complex n × n matrices such that the ring commutator [A, B] = AB – BA is \"small\" for each A ∈ A and B ∈ ℬ; does this imply that A and ℬ have a common non-trivial invariant subspace? This question is motivated by a series of papers studying the structure of \"almost-commutative\" algebras and, more generally, semigroups. A simple example shows that, in general, the answer is no: it may happen that the algebra ℬ is equal to the commutant A' of A and the two algebras do not share an invariant subspace. We characterize all such algebras: if a matrix algebra A does not share invariant subspaces with its commutant, then it must be similar to an amplification of a full matrix algebra. Then, we show that if A and ℬ are two algebras such that rank[A, B] ≤ 1 for all A ∈ A and B ∈ ℬ and the rank-one is achieved, then A and ℬ have a common invariant subspace. A number of partial results about linear spaces (rather than algebras) of matrices, as well as the condition that [A, B] is always nilpotent, are also discussed.

It is easy to see that if G\\mathcal {G} is a non-abelian group of unitary matrices, then for no members AA and BB of G\\mathcal {G} can the rank of AB−BAAB-BA be one. We examine the consequences of the assumption that this rank is at most two for a general semigroup S\\mathcal {S} of linear operators. Our conclusion is that under obviously necessary, but trivial, size conditions, S\\mathcal {S} is reducible. In the case of a unitary group satisfying the hypothesis, we show that it is contained in the direct sum G1⊕G2\\mathcal {G}_1\\oplus \\mathcal {G}_2, where G1\\mathcal {G}_1 is at most 3×33\\times 3 and G2\\mathcal {G}_2 is abelian.

It is easy to see that if \\(\\cG\\) is a non-abelian group of unitary matrices, then for no members \\(A\\) and \\(B\\) of \\(\\cG\\) can the rank of \\(AB-BA\\) be one. We examine the consequences of the assumption that this rank is at most two for a general semigroup \\(\\cS\\) of linear operators. Our conclusion is that under obviously necessary, but trivial, size conditions, \\(\\cS\\) is reducible. In the case of a unitary group satisfying the hypothesis, we show that it is contained in the direct sum \\(\\cG_1\\oplus\\cG_2\\) where \\(\\cG_1\\) is at most \\(3\\times 3\\) and \\(\\cG_2\\) is abelian.