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Isolating tissue-resident cells runs the risk of altering their expression profile. Jung and colleagues use a RiboTagging approach to describe the microglial translatome and demonstrate that macrophage extraction from their tissue environment results in significant transcriptional alterations.
Sixt, Stein and colleagues show that during T cell migration within lymphatic organs, the chemokine receptor CCR7 quantitatively controls the speed of a continuous actin flow, which is coupled to the environment by the integrin LFA-1.
Influenza can occasionally result in life-threatening sequelae. Openshaw and colleagues describe the functional and transcriptional response to natural infection with influenza virus and find that a transition to an ‘anti-bacterial response’ is associated with more-severe symptoms.
CARD9 serves as an adaptor for C-type lectin receptor signaling. Xin Lin and colleagues show that CARD9 inhibits RelB-mediated IL-5 expression. The CARD9S12N mutant, prevalent in humans, cannot interact with RelB and promotes enhanced allergic responses to fungal pathogens.
Semaphorins play well-known roles in axon guidance. Kumanogoh and colleagues demonstrate that Semaphorin 6D cell-intrinsically activates anti-inflammatory macrophage polarization.
Carbohydrate-specific antibodies are typically thought to be of low affinity and produced by T cell–independent pathways. Wardemann and colleagues identify human memory B cells that can produce specific ‘affinity-matured’ antibodies to the O antigen of Klebsiella lipopolysaccharides.
McGaha and colleagues show that phagocytosis of apoptotic cells leads to activation of the transcription factor AhR and production of the cytokine IL-10 in phagocytes, in a manner dependent on the recognition of DNA.
D’Angelo and colleagues show that the nucleoporin Nup210 plays a specific role in naïve CD4+ T cell homeostasis by regulating expression of Caveolin-2, which is required for tonic TCR signaling.
Dyslipidemia and autoimmune disease are often associated. Chung and colleagues demonstrate a mechanistic pathway by which dyslipidemia leads to the induction of pathogenic autoantibodies.
Lynch, Brenner and colleagues find that tissue-resident γδ T cells reside in adipose tissues in both mice and humans. These cells play essential roles in regulating thermogenesis and supporting age-dependent increases in adipose-tissue regulatory T cell populations.
Macrophages can be an important niche for chronic viral infection. Walker and colleagues demonstrate that macrophages are intrinsically resistant to CTL-mediated killing and can thereby contribute to the maintenance of HIV reservoirs and chronic inflammation.
Meningeal vascular damage accompanies mild traumatic brain injury, which persists in a fraction of patients. McGavern and colleagues report that distinct myeloid cell subsets are temporally recruited to the wound site during tissue repair; however, re-injury at early time points impairs recovery.
Harris and colleagues show that the cytokine TGF-β is required for colonization of the microglial niche and maintenance of central nervous system integrity. Acute loss of TGF-β leads to proinflammatory responses and fatal demyelinating disease.
Higher-order TCRs have been postulated to maintain high antigen sensitivity and trigger signaling. Huppa and colleagues use various investigative techniques and find exclusively monomeric TCR–CD3 complexes that drive the recognition of antigenic pMHC.
The transcription factor c-Maf controls IL-10 production in T cells. O’Garra and colleagues use systems and in vivo functional analysis of T cell subsets to reveal distinct context-specific roles for c-Maf.
NK cells constrain infection by cytomegalovirus. Romagnani and colleagues show that human NKG2C+ NK cells recognize distinct HCMV UL40 viral peptides, which can vary among viral isolates. NKG2C+ NK cells thereby demonstrate adaptive-like recognition that can discriminate between closely related viral strains.
Act1 is an adaptor protein that associates with the IL-17 receptor at the cell membrane. Li and colleagues show that Act1 also exhibits unexpected RNA-binding activity and directly stabilizes select mRNAs encoding inflammatory cytokines and chemokines.
The cytokine IL-33 has major roles in type 2 immunity and allergy. Girard and colleagues demonstrate that a broad range of allergens across multiple kingdoms can directly cleave IL-33 via their intrinsic protease activity and convert it into a highly active processed form.
Sander and colleagues show that antigen-presenting cells detect bacterial RNA from live bacteria via TLR8 and promote TFH cell differentiation and vaccine responses through the induction of a specific cytokine profile.
Tumor cells commonly manipulate their environment to ensure their survival. Kuan and Ziegler show that breast cancer cells release IL-1α, which acts on infiltrating myeloid cells to elicit their production of TSLP. In turn, TSLP promotes the survival of TSLPR+ tumor cells by upregulating expression of the pro-survival factor Bcl-2.