CD5 Instructs Extrathymic Regulatory T Cell Development in Response to Self and Tolerizing Antigens

Henderson, Jacob G.; Opejin, Adeleye; Jones, Andrew; Gross, Cindy; Hawiger, Daniel

doi:10.1016/j.immuni.2015.02.010

Cited by 93 publications

(116 citation statements)

References 61 publications

(143 reference statements)

Supporting

Mentioning

107

Contrasting

Order By: Relevance

“…A recent study showed that CD5 facilitates the extrathymic differentiation of pTreg cells by blocking mTORdependent signals induced by effector-differentiating cytokines that otherwise inhibit Treg cell induction (35). However, our results showed that Treg/Tconv differential response was not due to CD5 expression.…”

Section: Discussioncontrasting

confidence: 81%

“…Consistent with the correlation between CD5 expression and TCR signal strength, expression of CD5 is comparatively high in Treg cells (35,44). A recent study showed that CD5 facilitates the extrathymic differentiation of pTreg cells by blocking mTORdependent signals induced by effector-differentiating cytokines that otherwise inhibit Treg cell induction (35).…”

Section: Discussionmentioning

confidence: 57%

“…33). The amount of CD5 displayed on the cell surface is proportional to the intensity of signals received through the TCR, and CD5 is robustly expressed on Treg cells (34,35). To test whether CD5 more specifically inhibits signaling in Treg cells, we analyzed Erk phosphorylation after CD3/CD28 cross-linking across five matched ranges of surface CD5 (Fig.…”

Section: Significancementioning

confidence: 99%

See 2 more Smart Citations

Imbalanced signal transduction in regulatory T cells expressing the transcription factor FoxP3

Yan

Farache

Mingueneau

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

FoxP3+ T regulatory (Treg) cells have a fundamental role in immunological tolerance, with transcriptional and functional phenotypes that demarcate them from conventional CD4+ T cells (Tconv). Differences between these two lineages in the signaling downstream of T-cell receptor-triggered activation have been reported, and there are different requirements for some signaling factors. Seeking a comprehensive view, we found that Treg cells have a broadly dampened activation of several pathways and signaling nodes upon TCR-mediated activation, with low phosphorylation of CD3ζ, SLP76, Erk1/2, AKT, or S6 and lower calcium flux. In contrast, STAT phosphorylation triggered by interferons, IL2 or IL6, showed variations between Treg and Tconv in magnitude or choice of preferential STAT activation but no general Treg signaling defect. Much, but not all, of the Treg/Tconv difference in TCR-triggered responses could be attributed to lower responsiveness of antigen-experienced cells with CD44hi or CD62Llo phenotypes, which form a greater proportion of the Treg pool. Candidate regulators were tested, but the Treg/Tconv differential could not be explained by overexpression in Treg cells of the signaling modulator CD5, the coinhibitors PD-1 and CTLA4, or the regulatory phosphatase DUSP4. However, transcriptome profiling in Dusp4-deficient mice showed that DUSP4 enhances the expression of a segment of the canonical Treg transcriptional signature, which partially overlaps with the TCR-dependent Treg gene set. Thus, Treg cells, likely because of their intrinsically higher reactivity to self, tune down TCR signals but seem comparatively more attuned to cytokines or other intercellular signals.

show abstract

Section: Discussioncontrasting

confidence: 81%

Section: Discussionmentioning

confidence: 57%

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Imbalanced signal transduction in regulatory T cells expressing the transcription factor FoxP3

Yan

Farache

Mingueneau

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…CD5 expression is notably higher in T-cell subpopulations with regulatory or suppressive functions, i.e. in regulatory T (Treg) cells [41] suggesting that it may regulate their generation and/or function [42][43][44]. Similarly, CD5 is also highly expressed by regulatory B (Breg) cells [45], in which CD5 expression is required for autocrine IL-10 production.…”

mentioning

confidence: 99%

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

et al. 2017

View full text Add to dashboard Cite

Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. This scavenging activity makes SRs important molecules for host defense and homeostasis. In turn, SRs keep the activation of the steady-state immune response in check, and participate as co-receptors in the priming of the effector immune responses when the macromolecules are associated with a threat that might compromise host homeostasis. Therefore, SRs built up sophisticated sensor mechanisms controlling the immune system, which may be exploited to develop novel drugs for cancer immunotherapy. In this review, we focus on the regulation of the anti-tumor immune response by two paradigmatic SRs: the lymphocyte receptor CD5 and the more broadly distributed scavenger receptor class B type 1 (SR-B1). Cancer immunity can be boosted by blockade of SRs working as immune checkpoint inhibitors (CD5) and/or by proper engagement of SRs working as innate danger receptor (SR-B1). Thus, these receptors illustrate both the complexity of targeting SRs in cancer immunotherapy and also the opportunities offered by such an approach. Keywords:Cancer immunotherapy r CD5 r Danger signal r Immune-checkpoint r Scavenger receptor r Scavenger receptor class B type 1 r Toll-like receptors IntroductionThe cancer-immunity cycle can be subverted by tumors at many steps, thus novel therapeutic interventions should be considered for all these possibilities [1]. This cycle starts with the release of tumor antigens and their subsequent capture by professional antigen-presenting cells (mainly, dendritic cells; DCs) for the activation of effector cells of the innate and adaptive immune Correspondence: Dr. Pedro Berraondo e-mail: pberraondol@unav.es system. This is a highly regulated process aimed at maintaining the integrity of the host without inducing significant side effects (e.g., inflammation or autoimmunity) [2]. Tissue homeostasis involves phagocytic processes to remove the excess of native or modified molecules from unviable or stressed cells, as well as from invading microbial agents [3]. Such molecules include lipids, whose intracellular levels should be carefully controlled to sustain proper cell metabolism; endogenous glyco-and lipo-proteins, damaged or * These authors contributed equally to this work. * * These authors are senior co-authors of this work. [4,5]. This phagocytic activity should be coupled to an alarm signal system that awakens other effector mechanisms of the immune system when the tissue damage cannot be controlled by the removal of the endogenous or exogenous molecules. To this end, the immune system has a myriad of specialized soluble or membrane-bound receptors called pattern recognition receptors (PRRs). These PRRs are non-polymorphic, nonclonally distributed, and germ-line encoded receptors recognizing microorganism-associated molecular patterns (MAMPs) -tha...

show abstract

“…In this issue of Immunity, Henderson et al (2015) show that CD5 regulates iTreg cell induction by rendering emerging iTreg cells refractory to signals mediated by effector-differentiating cytokines.…”

mentioning

confidence: 99%

CD5 Helps Aspiring Regulatory T Cells Ward Off Unwelcome Cytokine Advances

Palin

Love

2015

Immunity

View full text Add to dashboard Cite

show abstract

CD5 Instructs Extrathymic Regulatory T Cell Development in Response to Self and Tolerizing Antigens

Cited by 93 publications

References 61 publications

Imbalanced signal transduction in regulatory T cells expressing the transcription factor FoxP3

Imbalanced signal transduction in regulatory T cells expressing the transcription factor FoxP3

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

CD5 Helps Aspiring Regulatory T Cells Ward Off Unwelcome Cytokine Advances

Contact Info

Product

Resources

About