Mind the GAP: RASA2 and RASA3 GTPase-activating proteins as gatekeepers of T cell activation and adhesion
Trends Immunol. 2023 Oct 17:S1471-4906(23)00194-1. doi: 10.1016/j.it.2023.09.002. Online ahead of print.ABSTRACTFollowing stimulation, the T cell receptor (TCR) and its coreceptors integrate multiple intracellular signals to initiate T cell proliferation, migration, gene expression, and metabolism. Among these signaling molecules are the small GTPases RAS and RAP1, which induce MAPK pathways and cellular adhesion to activate downstream effector functions. Although many studies have helped to elucidate the signaling intermediates that mediate T cell activation, the molecules and pathways that keep naive T cells in check are...
Source: Trends in Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Kristoffer H Johansen Dominic P Golec Klaus Okkenhaug Pamela L Schwartzberg Source Type: research
Mind the GAP: RASA2 and RASA3 GTPase-activating proteins as gatekeepers of T cell activation and adhesion
Trends Immunol. 2023 Oct 17:S1471-4906(23)00194-1. doi: 10.1016/j.it.2023.09.002. Online ahead of print.ABSTRACTFollowing stimulation, the T cell receptor (TCR) and its coreceptors integrate multiple intracellular signals to initiate T cell proliferation, migration, gene expression, and metabolism. Among these signaling molecules are the small GTPases RAS and RAP1, which induce MAPK pathways and cellular adhesion to activate downstream effector functions. Although many studies have helped to elucidate the signaling intermediates that mediate T cell activation, the molecules and pathways that keep naive T cells in check are...
Source: Trends in Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Kristoffer H Johansen Dominic P Golec Klaus Okkenhaug Pamela L Schwartzberg Source Type: research
On developmental programming of the immune system
Trends Immunol. 2023 Oct 16:S1471-4906(23)00196-5. doi: 10.1016/j.it.2023.09.004. Online ahead of print.ABSTRACTEarly-life environmental exposures play a significant role in shaping long-lasting immune phenotypes and disease susceptibility. Nevertheless, comprehensive understanding of the developmental programming of immunity is limited. We propose that the vertebrate immune system contains durable programmable components established through early environmental interactions and maintained in a stable and homeostatic manner. Some immune components, such as immunological memory, are intrinsically programmable. Others are inf...
Source: Trends in Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Jun Young Hong Ruslan Medzhitov Source Type: research
On developmental programming of the immune system
Trends Immunol. 2023 Oct 16:S1471-4906(23)00196-5. doi: 10.1016/j.it.2023.09.004. Online ahead of print.ABSTRACTEarly-life environmental exposures play a significant role in shaping long-lasting immune phenotypes and disease susceptibility. Nevertheless, comprehensive understanding of the developmental programming of immunity is limited. We propose that the vertebrate immune system contains durable programmable components established through early environmental interactions and maintained in a stable and homeostatic manner. Some immune components, such as immunological memory, are intrinsically programmable. Others are inf...
Source: Trends in Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Jun Young Hong Ruslan Medzhitov Source Type: research
Human macrophages choreograph tissue development
Trends Immunol. 2023 Oct 11:S1471-4906(23)00206-5. doi: 10.1016/j.it.2023.09.010. Online ahead of print.ABSTRACTYolk sac-derived macrophages have been described to promote organogenesis and tissue function in animal models, but the relevance of these studies for humans has been debated. Wang et al. reveal that human macrophage development follows similar developmental trajectories with functionally distinct macrophage populations across tissues as observed in mice.PMID:37833121 | DOI:10.1016/j.it.2023.09.010 (Source: Trends in Immunology)
Source: Trends in Immunology - October 13, 2023 Category: Allergy & Immunology Authors: Elvira Mass Source Type: research
Human macrophages choreograph tissue development
Trends Immunol. 2023 Oct 11:S1471-4906(23)00206-5. doi: 10.1016/j.it.2023.09.010. Online ahead of print.ABSTRACTYolk sac-derived macrophages have been described to promote organogenesis and tissue function in animal models, but the relevance of these studies for humans has been debated. Wang et al. reveal that human macrophage development follows similar developmental trajectories with functionally distinct macrophage populations across tissues as observed in mice.PMID:37833121 | DOI:10.1016/j.it.2023.09.010 (Source: Trends in Immunology)
Source: Trends in Immunology - October 13, 2023 Category: Allergy & Immunology Authors: Elvira Mass Source Type: research
Human macrophages choreograph tissue development
Trends Immunol. 2023 Oct 11:S1471-4906(23)00206-5. doi: 10.1016/j.it.2023.09.010. Online ahead of print.ABSTRACTYolk sac-derived macrophages have been described to promote organogenesis and tissue function in animal models, but the relevance of these studies for humans has been debated. Wang et al. reveal that human macrophage development follows similar developmental trajectories with functionally distinct macrophage populations across tissues as observed in mice.PMID:37833121 | DOI:10.1016/j.it.2023.09.010 (Source: Trends in Immunology)
Source: Trends in Immunology - October 13, 2023 Category: Allergy & Immunology Authors: Elvira Mass Source Type: research
Human macrophages choreograph tissue development
Trends Immunol. 2023 Oct 11:S1471-4906(23)00206-5. doi: 10.1016/j.it.2023.09.010. Online ahead of print.ABSTRACTYolk sac-derived macrophages have been described to promote organogenesis and tissue function in animal models, but the relevance of these studies for humans has been debated. Wang et al. reveal that human macrophage development follows similar developmental trajectories with functionally distinct macrophage populations across tissues as observed in mice.PMID:37833121 | DOI:10.1016/j.it.2023.09.010 (Source: Trends in Immunology)
Source: Trends in Immunology - October 13, 2023 Category: Allergy & Immunology Authors: Elvira Mass Source Type: research
IL-2-driven CD8 < sup > + < /sup > T cell phenotypes: implications for immunotherapy
Trends Immunol. 2023 Oct 10:S1471-4906(23)00195-3. doi: 10.1016/j.it.2023.09.003. Online ahead of print.ABSTRACTThe therapeutic potential of interleukin (IL)-2 in cancer treatment has been known for decades, yet its widespread adoption in clinical practice remains limited. Recently, chimeric proteins of an anti-PD-1 antibody and suboptimal IL-2 variants were shown to stimulate potent antitumor and antiviral immunity by inducing unique effector CD8+ T cells in mice. A similar subset of cytotoxic T cells is induced by depletion of regulatory T cells (Tregs), suggesting IL-2 sequestration as a major mechanism through which re...
Source: Trends in Immunology - October 12, 2023 Category: Allergy & Immunology Authors: Veronika Niederlova Oksana Tsyklauri Marek Kovar Ondrej Stepanek Source Type: research
IL-2-driven CD8 < sup > + < /sup > T cell phenotypes: implications for immunotherapy
Trends Immunol. 2023 Oct 10:S1471-4906(23)00195-3. doi: 10.1016/j.it.2023.09.003. Online ahead of print.ABSTRACTThe therapeutic potential of interleukin (IL)-2 in cancer treatment has been known for decades, yet its widespread adoption in clinical practice remains limited. Recently, chimeric proteins of an anti-PD-1 antibody and suboptimal IL-2 variants were shown to stimulate potent antitumor and antiviral immunity by inducing unique effector CD8+ T cells in mice. A similar subset of cytotoxic T cells is induced by depletion of regulatory T cells (Tregs), suggesting IL-2 sequestration as a major mechanism through which re...
Source: Trends in Immunology - October 12, 2023 Category: Allergy & Immunology Authors: Veronika Niederlova Oksana Tsyklauri Marek Kovar Ondrej Stepanek Source Type: research
Interplay between epigenetic and genetic alterations in inborn errors of immunity
Trends Immunol. 2023 Oct 7:S1471-4906(23)00197-7. doi: 10.1016/j.it.2023.09.005. Online ahead of print.ABSTRACTInborn errors of immunity (IEIs) comprise a variety of immune conditions leading to infections, autoimmunity, allergy, and cancer. Some IEIs have no identified mutation(s), while others with identical mutations can display heterogeneous presentations. These observations suggest the involvement of epigenetic mechanisms. Epigenetic alterations can arise from downstream activation of cellular pathways through both extracellular stimulation and genetic-associated changes, impacting epigenetic enzymes or their interact...
Source: Trends in Immunology - October 9, 2023 Category: Allergy & Immunology Authors: Javier Rodr íguez-Ubreva Celia L Calvillo Lisa R Forbes Satter Esteban Ballestar Source Type: research
Unleashing dendritic cell-mediated tumor clearance by targeting Bcl-2
Trends Immunol. 2023 Oct 7:S1471-4906(23)00203-X. doi: 10.1016/j.it.2023.09.007. Online ahead of print.ABSTRACTBcl-2 family proteins serve as key regulators of apoptosis and are frequently overexpressed in cancer. Consequently, small-molecule Bcl-2-antagonists (BH3 mimetics) have emerged as a new class of targeted therapeutics. A recent study by Zhao et al. has unexpectedly found that BH3 mimetics can also activate dendritic cells (DCs) to prime for T cell-mediated tumor clearance.PMID:37813733 | DOI:10.1016/j.it.2023.09.007 (Source: Trends in Immunology)
Source: Trends in Immunology - October 9, 2023 Category: Allergy & Immunology Authors: Seamus J Martin Source Type: research
Interplay between epigenetic and genetic alterations in inborn errors of immunity
Trends Immunol. 2023 Oct 7:S1471-4906(23)00197-7. doi: 10.1016/j.it.2023.09.005. Online ahead of print.ABSTRACTInborn errors of immunity (IEIs) comprise a variety of immune conditions leading to infections, autoimmunity, allergy, and cancer. Some IEIs have no identified mutation(s), while others with identical mutations can display heterogeneous presentations. These observations suggest the involvement of epigenetic mechanisms. Epigenetic alterations can arise from downstream activation of cellular pathways through both extracellular stimulation and genetic-associated changes, impacting epigenetic enzymes or their interact...
Source: Trends in Immunology - October 9, 2023 Category: Allergy & Immunology Authors: Javier Rodr íguez-Ubreva Celia L Calvillo Lisa R Forbes Satter Esteban Ballestar Source Type: research
Unleashing dendritic cell-mediated tumor clearance by targeting Bcl-2
Trends Immunol. 2023 Oct 7:S1471-4906(23)00203-X. doi: 10.1016/j.it.2023.09.007. Online ahead of print.ABSTRACTBcl-2 family proteins serve as key regulators of apoptosis and are frequently overexpressed in cancer. Consequently, small-molecule Bcl-2-antagonists (BH3 mimetics) have emerged as a new class of targeted therapeutics. A recent study by Zhao et al. has unexpectedly found that BH3 mimetics can also activate dendritic cells (DCs) to prime for T cell-mediated tumor clearance.PMID:37813733 | DOI:10.1016/j.it.2023.09.007 (Source: Trends in Immunology)
Source: Trends in Immunology - October 9, 2023 Category: Allergy & Immunology Authors: Seamus J Martin Source Type: research
Interplay between epigenetic and genetic alterations in inborn errors of immunity
Trends Immunol. 2023 Oct 7:S1471-4906(23)00197-7. doi: 10.1016/j.it.2023.09.005. Online ahead of print.ABSTRACTInborn errors of immunity (IEIs) comprise a variety of immune conditions leading to infections, autoimmunity, allergy, and cancer. Some IEIs have no identified mutation(s), while others with identical mutations can display heterogeneous presentations. These observations suggest the involvement of epigenetic mechanisms. Epigenetic alterations can arise from downstream activation of cellular pathways through both extracellular stimulation and genetic-associated changes, impacting epigenetic enzymes or their interact...
Source: Trends in Immunology - October 9, 2023 Category: Allergy & Immunology Authors: Javier Rodr íguez-Ubreva Celia L Calvillo Lisa R Forbes Satter Esteban Ballestar Source Type: research
