MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4

Walsh, James T.; Hendrix, Sven; Boato, Francesco; Smirnov, Igor; Zheng, Jingjing; Lukens, John R.; Gadani, Sachin P.; Hechler, Daniel; Gölz, Greta; Rosenberger, Karen; Kammertöns, Thomas; Vogt, Johannes; Vogelaar, Christina Francisca; Siffrin, Volker; Radjavi, Ali; Fernández-Castañeda, Anthony; Gaultier, Alban; Gold, Ralf; Kanneganti, Thirumala‐Devi; Nitsch, Robert; Zipp, Frauke; Kipnis, Jonathan

doi:10.1172/jci82458

Cited by 67 publications

(63 citation statements)

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“…IL-4 and type 2 immune responses are important for tissue repair and the production of the epidermal growth factor-like molecule amphiregulin (Zaiss et al, 2015), which can be present in atypical CD8 cells in the skin (Harrison et al, 2019). IL-4 also can act on neurons to promote axonal repair in the setting of neuroinflammation (Vogelaar et al, 2018;Walsh et al, 2015), and moreover, type 2 cytokines including IL-4 also directly activate sensory neurons that elicit itch responses. Patients with chronic itch improve when treated with JAK inhibitors, and this is believed to occur based on the inhibition of IL-4 signaling (Oetjen et al, 2017).…”

Section: Nonclassical Views Of G C Cytokinesmentioning

confidence: 99%

The γc Family of Cytokines: Basic Biology to Therapeutic Ramifications

2019

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The common cytokine receptor g chain, g c , is a component of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. Mutation of the gene encoding g c results in X-linked severe combined immunodeficiency in humans, and g c family cytokines collectively regulate development, proliferation, survival, and differentiation of immune cells. Here, we review the basic biology of these cytokines, highlighting mechanisms of signaling and gene regulation that have provided insights for immunodeficiency, autoimmunity, allergic diseases, and cancer. Moreover, we discuss how studies of this family stimulated the development of JAK3 inhibitors and present an overview of current strategies targeting these pathways in the clinic, including novel antibodies, antagonists, and partial agonists. The diverse roles of these cytokines on a range of immune cells have important therapeutic implications.

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Section: Nonclassical Views Of G C Cytokinesmentioning

confidence: 99%

The γc Family of Cytokines: Basic Biology to Therapeutic Ramifications

2019

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“…These beneficial effects could be the result of the increase in antiinflammatory and regeneration‐associated proteins as well as the reduction of pro‐inflammatory molecules which contribute inducing a favorable microenvironment for neurogenic processes. There was a significant increase in IL‐4 and IL‐10 which are strongly related to neuroprotective and regenerative actions as well as with axon elongation 31 …”

Section: Discussionmentioning

confidence: 96%

Immunization with neural‐derived peptides increases neurogenesis in rats with chronic spinal cord injury

et al. 2020

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Aims Immunization with neural‐derived peptides (INDP) has demonstrated to be a promising therapy to achieve a regenerative effect in the chronic phase of the spinal cord injury (SCI). Nevertheless, INDP‐induced neurogenic effects in the chronic stage of SCI have not been explored. Methods and Results In this study, we analyzed the effect of INDP on both motor and sensitive function recovery; afterward, we assessed neurogenesis and determined the production of cytokines (IL‐4, IL‐10, and TNF alpha) and neurotrophic factors (BDNF and GAP‐43). During the chronic stage of SCI, rats subjected to INDP showed a significant increase in both motor and sensitive recovery when compared to the control group. Moreover, we found a significant increase in neurogenesis, mainly at the central canal and at both the dorsal and ventral horns of INDP‐treated animals. Finally, INDP induced significant production of antiinflammatory and regeneration‐associated proteins in the chronic stages of SCI. Conclusions These findings suggest that INDP has a neurogenic effect that could improve motor and sensitive recovery in the chronic stage of SCI. Moreover, our results also envision the use of INDP as a possible therapeutic strategy for other trauma‐related disorders like traumatic brain injury.

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“…Inclusive, adoptive transfer of producing-IL-4, IL-10 and IL-3 CNS activated lymphocytes balance local inflammatory microenvironment by increasing protective cell populations like CD4 + /Foxp3 + and CD68 + /Arg1 + cells and in situ, proving that an increment of Th2 subset is beneficial to CNS repair [97,101,102]. But, increasing Treg population most be taking in consideration, due to injection of Treg can increase suppressive functions and limit effector T lymphocytes, which is negative to injured tissue in an optic nerve injury model [103].…”

Section: Lymphocyte Transferring After Scimentioning

confidence: 99%

Transplantation or Transference of Cultured Cells as a Treatment for Spinal Cord Injury

Rodríguez-Barrera¹,

Soria-Zavala²,

García–Sánchez³

et al. 2019

Spinal Cord Injury Therapy [Working Title]

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Spinal cord injury (SCI) involves damage to the spinal cord causing both structural and functional changes, which can lead to temporary or permanent alterations. Even though there have been many advances in its treatment, the results of clinical trials suggest that the current therapies are not sufficiently effective.Recently, there has been a lot of interest in regulating this harmful environment by transplanting cultured cells and boosting their antiinflammatory cytokines and growth factors production. Several types of cells have been studied for SCI therapy including, Schwann cells (SC's), olfactory ensheathing cells (OECs), choroid plexus epithelial cells (CPECs), and immune cells (ICs) (lymphocytes, dendritic cells and alternative macrophage and microglia phenotypes). These treatments have shown to be promising and in this chapter, we will review the general aspects of transplanting these cells for SCI therapy as well as the neuroprotective and regenerative responses that different types of cells have reached in different SCI models. The mesenchymal stem cells (MSC) are one of the most well studied cell types; however, they were not included in this section because they will be reviewed in another chapter of this book.

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MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4

Abstract: A r t i c l e A m e n d m e n t s2 5 4 7

Cited by 67 publications

References 0 publications

The γc Family of Cytokines: Basic Biology to Therapeutic Ramifications

The γc Family of Cytokines: Basic Biology to Therapeutic Ramifications

Immunization with neural‐derived peptides increases neurogenesis in rats with chronic spinal cord injury

Transplantation or Transference of Cultured Cells as a Treatment for Spinal Cord Injury

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