Nature Immunology Contents: February 2017 Volume 18 pp 115 - 246

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February 2017 Volume 18, Issue 2

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Focus on Neuroimmune communication
Neuroimmune communication   p115
We present a special set of Review articles on neuroimmune communication that highlight how the immune system and nervous system are anatomically connected, mechanistically communicate and reciprocally influence the other's function.



Focus on Neuroimmune communication
Neuroimmune regulation during intestinal development and homeostasis   pp116 - 122
Henrique Veiga-Fernandes and Vassilis Pachnis
Enteric neurons and intestinal immune cells co-develop in response to common cues and communicate with each other to maintain organ function and host defense.

Focus on Neuroimmune communication
The movers and shapers in immune privilege of the CNS   pp123 - 131
Britta Engelhardt, Peter Vajkoczy and Roy O Weller
Engelhardt and colleagues review barriers separating blood from CSF and CNS parenchyma, how pathways draining solutes from CNS to lymph nodes exclude trafficking of antigen-presenting cells and how intravital microscopy has influenced debate on immune privilege of the CNS.

Focus on Neuroimmune communication
Infectious immunity in the central nervous system and brain function   pp132 - 141
Robyn S Klein, Charise Garber and Nicole Howard
Various neurotrophic pathogens are capable of infecting CNS tissues. Klein and colleagues review how immune responses and inflammation in the CNS affect brain function and mental status.

News and Views


Is sex bias orchestrated in the skin?   pp142 - 143
Aridaman Pandit, Linde Meyaard and Timothy R D J Radstake
The identification of VGLL3 as a transcription (co-)factor that underlies the sex bias of the human immune system further underscores the relevance of research into this area.

See also: Article by Liang et al.

Epigenetic orchestration of thymic Treg cell development   pp144 - 146
Marc Beyer and Jochen Huehn
Regulatory T cells develop in the thymus as a distinct lineage of T cells instructed by the lineage-specifying transcription factor Foxp3. Epigenetic imprinting by the genome organizer Satb1 precedes this cell-fate 'decision' during thymocyte development.

See also: Article by Kitagawa et al.

RNA-binding proteins mind the GAPs   pp146 - 148
Martin Turner and Elisa Monzón-Casanova
Increased expression of the ubiquitin ligase TRAF6 in hematopoietic stem cells promotes activity of the GTP-binding protein Cdc42 and consequent diminished function of hematopoietic stem cells by ubiquitination of the RNA-binding protein hnRNP-A1, which leads to an inability to properly process pre-mRNA encoding Cdc42-inhibitory GTPase-activating proteins.

See also: Article by Fang et al.

iNKT cells need UTX-tra demethylation   pp148 - 150
S Harsha Krovi and Laurent Gapin
The epigenetic regulation of gene expression by the histone demethylase UTX is central to the development of invariant natural killer cells.

See also: Article by Beyaz et al.

JOBS of the week
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Research Highlights


Fasting fights leukemia | The interferon signature | Keeping IgE+ B cells under wraps | Keeping your T cells | Neurologic Mtb-HIV complications | Neurophils aid successful pregnancy



A gene network regulated by the transcription factor VGLL3 as a promoter of sex-biased autoimmune diseases   pp152 - 160
Yun Liang, Lam C Tsoi, Xianying Xing, Maria A Beamer, William R Swindell et al.
Various autoimmune diseases have sex-linked biases. Gudjonsson and colleagues find that the transcription factor VGLL3 is associated with a female-biased molecular signature linked to susceptibility to autoimmune disease.

See also: News and Views by Pandit et al.

Transcriptional programs that control expression of the autoimmune regulator gene Aire   pp161 - 172
Yonatan Herzig, Shir Nevo, Chamutal Bornstein, Miriam R Brezis, Sharon Ben-Hur et al.
Abramson and colleagues show that the coordinated action of several transcriptional regulators, including Irf4, Irf8, Tbx21, Tcf7 and Ctcfl, acts on medullary-thymic-epithelial-cell-specific accessible regions in the locus encoding the transcriptional regulator Aire to control its expression.

Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment   pp173 - 183
Yohko Kitagawa, Naganari Ohkura, Yujiro Kidani, Alexis Vandenbon, Keiji Hirota et al.
Thymic regulatory T (Treg) precursors undergo a distinct developmental pathway. Sakaguchi and colleagues show the chromatin organizer Satb1 is required for establishing the super-enhancer chromatin landscape of Treg cell-specific signature genes before Foxp3 expression.

See also: News and Views by Beyer & Huehn

The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells   pp184 - 195
Semir Beyaz, Ji Hyung Kim, Luca Pinello, Michael E Xifaras, Yu Hu et al.
Natural killer T cells in the thymus are CD1d-restricted cells that are selected at the CD4+CD8+ double-positive stage and require a variety of transcription factors for their development. Orkin, Winau and colleagues show that the histone demethylase UTX serves an essential role in the transcriptional control of the thymic maturation of these cells through multiple epigenetic mechanisms.

See also: News and Views by Krovi & Gapin

Recruitment of calcineurin to the TCR positively regulates T cell activation   pp196 - 204
Debjani Dutta, Valarie A Barr, Itoro Akpan, Paul R Mittelstadt, Laishram I Singha et al.
The phosphatase calcineurin targets NFAT transcription factors in T cells. Ashwell and colleagues show that calcineurin is recruited to the TCR signaling complex, where it reverses the inhibitory phosphorylation of the kinase Lck.

Themis2 lowers the threshold for B cell activation during positive selection   pp205 - 213
Daian Cheng, Mukta Deobagkar-Lele, Ekaterina Zvezdova, Seeyoung Choi, Shoji Uehara et al.
Cornall and colleagues show that Themis2 interacts with the phospholipase PLC-γ2 and lowers the threshold for B cell activation by low but not high avidity antigens.

The ubiquitin E3 ligase TRIM31 promotes aggregation and activation of the signaling adaptor MAVS through Lys63-linked polyubiquitination   pp214 - 224
Bingyu Liu, Meng Zhang, Honglei Chu, Honghai Zhang, Haifeng Wu et al.
Sensors of RNA viruses trigger prion-like aggregation of the adaptor MAVS, which leads to antiviral responses. Gao and colleagues show that the E3 ligase TRIM31 positively regulates this process by K63-linked polyubiquitination of MAVS.

HIV-1 blocks the signaling adaptor MAVS to evade antiviral host defense after sensing of abortive HIV-1 RNA by the host helicase DDX3   pp225 - 235
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani et al.
Gringhuis, Geijtenbeek and colleagues show that the RNA helicase DDX3 binds abortive HIV-1 RNA and induces type I interferon in dendritic cells, a process that is inhibited by the HIV-1-induced activation of kinase PLK1.

Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia   pp236 - 245
Jing Fang, Lyndsey C Bolanos, Kwangmin Choi, Xiaona Liu, Susanne Christie et al.
Starczynowski and colleagues show that overexpression of TRAF6 in HSCs induces ubiquitination of the RNA-binding protein hnRNPA1 and alternative splicing of Arhgap1, which accounts for the hematopoietic defects in myelodysplastic syndromes.

See also: News and Views by Turner & Monzon-Casanova



Corrigendum: WNK1 kinase balances T cell adhesion versus migration in vivo   p246
Robert Köchl, Flavian Thelen, Lesley Vanes, Tiago F Brazão, Kathryn Fountain et al.

Corrigendum: The role of the local environment and epigenetics in shaping macrophage identity and their effect on tissue homeostasis   p246
Ido Amit, Deborah R Winter and Steffen Jung



Erratum: Sall1 is a transcriptional regulator defining microglia identity and function   p246
Anne Buttgereit, Iva Lelios, Xueyang Yu, Melissa Vrohlings, Natalie R Krakoski et al.

Erratum: Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells   p246
Pleun Hombrink, Christina Helbig, Ronald A Backer, Berber Piet, Anna E Oja et al.

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