Focus 26 January 2021

Immunology

Immunology is a functional definition describing studies related to host protection mechanisms against pathogens, and is thus in itself a multi-disciplinary science linking topics such as biochemistry, cell biology, microbiology and disease. Here in this editorial page, we select articles that feel most exciting to us to share with you, and hope that you will feel the same.

Featured articles

OVOL2 sustains postnatal thymic epithelial cell identity

The molecular mechanisms that maintain thymic epithelial cell (TEC) identity throughout life are incompletely understood. Here, the authors demonstrate that the transcription factor, Ovol2, maintains post-natal TECs by preventing their epithelial-to-mesenchymal transition.
- Xue Zhong
- Nagesh Peddada
- Bruce Beutler
ArticleOpen Access27 Nov 2023 Nature Communications
A subset of type-II collagen-binding antibodies prevents experimental arthritis by inhibiting FCGR3 signaling in neutrophils

Rheumatoid arthritis (RA) involves several types of autoantibodies, which are usually considered pathogenic. In this study, the authors use phage display to develop antibodies targeting type-II collagen that are protective in multiple experimental models of RA.
- Zhongwei Xu
- Bingze Xu
- Rikard Holmdahl
ArticleOpen Access23 Sep 2023 Nature Communications
Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy

Immune checkpoint inhibitors (ICI) may have unanticipated side effects in transplant recipients who subsequently develop tumors. Here the authors used single-cell sequencing to identify and characterize allogeneic reactive T cells that developed after an ICI course for melanoma in a transplant recipient.
- Garrett S. Dunlap
- Daniel DiToro
- Deepak A. Rao
ArticleOpen Access21 Mar 2023 Nature Communications
Extracellular matrix educates an immunoregulatory tumor macrophage phenotype found in ovarian cancer metastasis

Although remodelling of the extracellular matrix (ECM) is associated with the establishment of an immunosuppressive tumour microenvironment, whether the ECM can educate tumor-associated macrophage phenotypes is not known. Here, the authors examine this question using decellularized tissue models of omental metastasis from patient biopsies.
- E. H. Puttock
- E. J. Tyler
- O. M. T. Pearce
ArticleOpen Access15 May 2023 Nature Communications
Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells

V gene recombination at the immunoglobulin heavy chain locus (Igh) is facilitated by extended loop extrusion. In this study, the authors find that, unlike Igh, the κ light chain locus does not involve extended loop extrusion but instead involves multiple, short-range loops for V gene combination.
- Louisa Hill
- Gordana Wutz
- Meinrad Busslinger
ArticleOpen Access21 Apr 2023 Nature Communications
RNA-binding protein RBM3 intrinsically suppresses lung innate lymphoid cell activation and inflammation partially through CysLT1R

The function of RNA binding proteins within innate lymphoid cells (ILC) has been partially characterised. Here the authors show that RBM3 functions to limit the type 2 immunity promoting activity of ILC2 partially through cysteinyl leukotriene 1 receptor.
- Jana H. Badrani
- Allyssa N. Strohm
- Taylor A. Doherty
ArticleOpen Access30 Jul 2022 Nature Communications
Context-dependent function of TSLP and IL-1β in skin allergic sensitization and atopic march

Allergic sensitisation in the skin can lead to allergic dermatitis and further to airway asthma in a process of atopic march. Here the authors examine the difference between superficial or deep skin sensitisation, characterise the immune cells generated and show differential TSLP and IL-1β involvement.
- Justine Segaud
- Wenjin Yao
- Mei Li
ArticleOpen Access1 Sep 2022 Nature Communications
The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation

The anti-viral protein MAVS forms aggregates as part of the antiviral response and promoting type I IFN responses. Here the authors show that protein arginine methyltransferase 9 (PRMT9) methylates MAVS to keep the protein in a non-aggregated state and propose a regulatory mechanism for MAVS.
- Xuemei Bai
- Chao Sui
- Chengjiang Gao
ArticleOpen Access26 Aug 2022 Nature Communications
Identification of distinct functional thymic programming of fetal and pediatric human γδ thymocytes via single-cell analysis

Knowledge about the ontogeny of T cells in the thymus relies heavily on mouse studies because of difficulty to obtain human material. Here the authors perform a single cell analysis of thymocytes from human fetal and paediatric thymic samples to characterise the development of human γδ T cells in the thymus.
- Guillem Sanchez Sanchez
- Maria Papadopoulou
- David Vermijlen
ArticleOpen Access4 Oct 2022 Nature Communications
Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation

The epithelial protein Coxsackievirus Adenovirus Receptor (CAR) is a virus receptor but may have other functions. Here the authors show that deletion of CAR in mice leads to reduced house dust mite-induced lung inflammation, reduced neutrophil accumulation and alterations in airway remodelling.
- Elena Ortiz-Zapater
- Dustin C. Bagley
- Maddy Parsons
ArticleOpen Access27 Oct 2022 Nature Communications
Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis

Antibodies directed against citrullinated proteins are commonly found in patients with rheumatoid arthritis. Here, the authors show that citrullination alters the peptide repertoire presented to T cells by altering protease cleavage and inducing protein destabilization, thereby exposing cryptic epitopes.
- Ashley M. Curran
- Alexander A. Girgis
- Erika Darrah
ArticleOpen Access24 Feb 2023 Nature Communications
On maternity and the stronger immune response in women

Women generally mount a stronger immune response to infections than men do, resulting in a higher impact of autoimmune diseases. Here, the authors show that pathogen transmission from mother-to-child during pregnancy drives the co-evolution of a stout defence against harmless pathogens in women.
- Evan Mitchell
- Andrea L. Graham
- Geoff Wild
ArticleOpen Access18 Aug 2022 Nature Communications
A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling

Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) is normally induced by innate immunity sensing for protection from pathogens. Here the authors show that cGAMP is also upstream of DNA damage signaling by activating ATM-CHK2-mediated repair pathway, while simultaneously suppressing the homology-directed repair.
- Daipayan Banerjee
- Kurt Langberg
- Nagaraj Kerur
ArticleOpen Access27 Oct 2021 Nature Communications
Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation

The transcription factor, IRF5, has been implicated in the regulation of inflammation, but how IRF5 protein is activated is still unclear. Here the authors use inhibitor library screening, biochemical analyses and in vivo/ex vivo data to show that a protein tyrosine kinase, Pyk2, may be key for the activation of IRF5 in macrophages and inflammatory responses in the gut.
- Grigory Ryzhakov
- Hannah Almuttaqi
- Irina A. Udalova
ArticleOpen Access18 Nov 2021 Nature Communications
Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers

A rare sub-population of people living with HIV-1 experience long-lasting viral remission after interrupting antiretroviral therapy and are considered post-treatment controllers. Here the authors characterise the humoral immune response to HIV-1 in a cohort of post-treatment controllers.
- Luis M. Molinos-Albert
- Valérie Lorin
- ANRS VISCONTI Study Group
ArticleOpen Access11 Apr 2022 Nature Communications
Candida albicans evades NK cell elimination via binding of Agglutinin-Like Sequence proteins to the checkpoint receptor TIGIT

Natural killer cells have emerged as critical immune cells in the response to fungal infection. Here the authors identify how Candida albicans evades the natural killer cell response via expression of ligands that directly modify the natural killer cell response and can be therapeutically targeted to restore the anti-Candida immunity.
- Yoav Charpak-Amikam
- Tom Lapidus
- Ofer Mandelboim
ArticleOpen Access5 May 2022 Nature Communications
Off-the-shelf CAR natural killer cells secreting IL-15 target spike in treating COVID-19

Severe COVID-19 requires immediate and targeted intervention that is efficient against SARS-CoV-2 and its variants. Authors show here the therapeutic potential of engineered natural killer cells that simultaneously express a chimeric antigen receptor targeting the spike protein of SARS-CoV-2, and IL-15, a cytokine that enhances the function and survival of their own.
- Ting Lu
- Rui Ma
- Jianhua Yu
ArticleOpen Access11 May 2022 Nature Communications
PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration

The Programmed death-1 (PD-1) and its ligand PD-L1 are critical checkpoints in the regulation of immune responses. Here the authors implicate PD-L1 signalling at lymphatic endothelium in the regulation of transendothelial migration of T cells.
- Wenji Piao
- Lushen Li
- Jonathan S. Bromberg
ArticleOpen Access21 Apr 2022 Nature Communications
Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer

Vaccination with BCG has been shown to induce a pre-priming effect in innate immune cells termed trained immunity. Here the authors re-engineer the BCG vaccine and show augmented immune responses, enhanced induction of trained immunity and improved antitumor efficacy in pre-clinical models of bladder cancer.
- Alok Kumar Singh
- Monali Praharaj
- Trinity J. Bivalacqua
ArticleOpen Access15 Feb 2022 Nature Communications
CD45 pre-exclusion from the tips of T cell microvilli prior to antigen recognition

CD45 limits T cell activation, so its exclusion from the T cell immunological synapse is thought to occur as a means to enable TCR signalling. Here the authors use a variety of cellular imaging methods to show that CD45 is indeed excluded from the tips of the T cell microvilli and that this occurs prior to contact with antigen, indicating this exclusion is one of the initiating factors for antigen presentation and T cell activation.
- Yunmin Jung
- Lai Wen
- Klaus Ley
ArticleOpen Access23 Jun 2021 Nature Communications
Lasp1 regulates adherens junction dynamics and fibroblast transformation in destructive arthritis

Fibroblast-like synoviocytes are important mediators of joint pathology in rheumatoid arthritis (RA). Here the authors show that Lasp1 is epigenetically regulated and highly expressed by these cells in RA and its deletion can limit joint pathology in a mouse model of inflammatory arthritis.
- Denise Beckmann
- Anja Römer-Hillmann
- Adelheid Korb-Pap
ArticleOpen Access15 Jun 2021 Nature Communications
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine

3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.
- Cristina C. Clement
- Angelo D’Alessandro
- Laura Santambrogio
ArticleOpen Access21 Jul 2021 Nature Communications
Chloride sensing by WNK1 regulates NLRP3 inflammasome activation and pyroptosis

The serine/threonine kinase WNK1 is an inhibitor of chloride efflux. Here the authors show that this inhibition is a means of negatively regulating the activation of the NLRP3 inflammasome in macrophages, leading to reduced inflammatory responses.
- Lindsey Mayes-Hopfinger
- Aura Enache
- Emad S. Alnemri
ArticleOpen Access27 Jul 2021 Nature Communications
Type II alveolar cell MHCII improves respiratory viral disease outcomes while exhibiting limited antigen presentation

Type II alveolar cells play central roles in multiple aspects of lung biology. Here the authors show that type II alveolar cells also constitutively express MHCII, exhibit limited MHCII antigen presentation capacity, and are a component of the host response to respiratory viral infection.
- Sushila A. Toulmin
- Chaitali Bhadiadra
- Laurence C. Eisenlohr
ArticleOpen Access28 Jun 2021 Nature Communications
The neutrotime transcriptional signature defines a single continuum of neutrophils across biological compartments

Differentiating neutrophil functional states is difficult. Here the authors show, using single cell RNA-sequencing and trajectory analyses, that mouse neutrophils can be presented as a transcriptome continuum rather than discrete subsets, but are affected by inflammation to express distinct transcriptional states.
- Ricardo Grieshaber-Bouyer
- Felix A. Radtke
- ImmGen Consortium
ArticleOpen Access17 May 2021 Nature Communications
GATA3 induces mitochondrial biogenesis in primary human CD4⁺ T cells during DNA damage

GATA3 has been considered to be primarily associated with CD4⁺ Th2 cell function. Using CD4⁺ effector memory that re-express CD45RA (EMRA) T cells the authors show that in response to DNA damage GATA3 can regulate increase of mitochondrial mass and biogenesis involving AMPK.
- Lauren A. Callender
- Johannes Schroth
- Sian M. Henson
ArticleOpen Access7 Jun 2021 Nature Communications
FcγR engagement reprograms neutrophils into antigen cross-presenting cells that elicit acquired anti-tumor immunity

Neutrophils are versatile immune cells that may also serve as antigen-presenting cells (APC). Here the authors show that engaging FcγRs on neutrophils with immune complexes or an anti-FcγR-antigen conjugate induces neutrophil APC with comparable functions as classical dendritic cells, and with therapeutic potentials for cancer and infectious diseases.
- Vijayashree Mysore
- Xavier Cullere
- Tanya N. Mayadas
ArticleOpen Access9 Aug 2021 Nature Communications
Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

Macrophages perform diverse functions during immune responses, but the molecular mechanisms by which physical properties of the tissue regulate macrophage behavior remain unknown. Here the authors find that Piezo1 is a mechanosensor of stiffness, and that its activity modulates macrophage polarization responses.
- Hamza Atcha
- Amit Jairaman
- Wendy F. Liu
ArticleOpen Access31 May 2021 Nature Communications
Cell barrier function of resident peritoneal macrophages in post-operative adhesions

Peritoneal adhesions are a major cause of complications after abdominal surgery. Here the authors use a post-operative abdominal adhesion model in mice to show that resident F4/80^HighCD206⁻ macrophages form a protective barrier that can be enhanced by IL-4 administration or adoptive transfer of these cells.
- Tomoya Ito
- Yusuke Shintani
- Ken Suzuki
ArticleOpen Access14 Apr 2021 Nature Communications
METTL3-dependent m⁶A modification programs T follicular helper cell differentiation

T follicular helper (T_FH) cells are specialized effector CD4⁺ T cells that are critical in humoral immunity, but the function of post-transcriptional regulation is not clearly defined. Here, the authors demonstrate that RNA methylation is important for T_FH effector differentiation and subsequent antibody formation through stabilization of Tcf7 transcripts.
- Yingpeng Yao
- Ying Yang
- Shuyang Yu
ArticleOpen Access26 Feb 2021 Nature Communications
Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy

Immune checkpoint inhibition (ICI) shows potential for cancer therapies, but response rates vary. Here, the authors use single-cell analyses to show that, in a 28 patient cohort, patients stratified by mucosal-associated invariant T (MAIT) percentages show different response rates, and ICI responders have more MAIT cells expressing CXCR4 and granzyme B.
- Sara De Biasi
- Lara Gibellini
- Andrea Cossarizza
ArticleOpen Access15 Mar 2021 Nature Communications
Transcriptome and chromatin landscape of iNKT cells are shaped by subset differentiation and antigen exposure

Invariant natural killer T cells are known to be composed of a number of phenotypic and functionally distinct populations. Here the authors use transcriptomic and epigenomic analysis to further characterize the peripheral iNKT compartment before and after antigenic stimulation.
- Mallory Paynich Murray
- Isaac Engel
- Mitchell Kronenberg
ArticleOpen Access4 Mar 2021 Nature Communications
Recruited macrophages that colonize the post-inflammatory peritoneal niche convert into functionally divergent resident cells

The peritoneal cavity is a complicated myeloid niche containing a mixed population of resident macrophages and infiltrating cells that are responsive to inflammatory cues. Here the authors trace the fate of these infiltrating macrophages, their conversion to resident cells and how this is altered by the local inflammatory state over time.
- P. A. Louwe
- L. Badiola Gomez
- S. J. Jenkins
ArticleOpen Access19 Mar 2021 Nature Communications
The neutrophil antimicrobial peptide cathelicidin promotes Th17 differentiation

Neutrophils secrete numerous immune effector molecules including cathelicidin which is associated with antimicrobial properties. Here the authors implicate neutrophil derived cathelicidin in modulation of CD4 T cell homoeostasis and the promotion of Th17 CD4 T cells.
- Danielle Minns
- Katie J. Smith
- Emily Gwyer Findlay
ArticleOpen Access24 Feb 2021 Nature Communications
Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children

Childhood infection with SARS CoV2 is associated with a milder course of infection but the immunopathogenesis of this remains unclear. Here the authors explore immunological differences in the innate immune system during acute and convalescent SARS CoV2 infection in the young.
- Melanie R. Neeland
- Samantha Bannister
- Richard Saffery
ArticleOpen Access17 Feb 2021 Nature Communications
A tetravalent live attenuated dengue virus vaccine stimulates balanced immunity to multiple serotypes in humans

Multivalent vaccines that confer protection to multiple serotypes of Dengue virus have been established. Here the authors examine the presence of vaccine induced multivalent antibodies and how these link to protection in a human challenge model of Dengue virus.
- Usha K. Nivarthi
- Jesica Swanstrom
- Aravinda M. de Silva
ArticleOpen Access17 Feb 2021 Nature Communications
Notch2-mediated plasticity between marginal zone and follicular B cells

Notch signalling is central to marginal zone B cell development, but it is unclear what path this development takes in vivo. Here the authors use a mouse that lacks these cells to show that transgenic induction of Notch2 is sufficient for development of marginal zone B cells via transdifferentiation from follicular B cells and that this mechanism can occur in wildtype mice.
- Markus Lechner
- Thomas Engleitner
- Ursula Zimber-Strobl
ArticleOpen Access17 Feb 2021 Nature Communications
Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation

Myeloid cells are able to utilize a variety of monosaccharides from our diet, including fructose. Here the authors show that when monocytes are reliant on fructose as a carbon energy source they are reprogrammed towards oxidative metabolism, glutamine anaplerosis and a pro-inflammatory phenotype owing to excess pro-inflammatory cytokine production.
- Nicholas Jones
- Julianna Blagih
- Catherine A. Thornton
ArticleOpen Access22 Feb 2021 Nature Communications
MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity

Mitochondrial antiviral signalling protein (MAVS) is an adaptor of RIG-I like receptor. Here the authors show that mitochondrial fission factor (Mff) is required for clustering of MAVS on the outer mitochondrial membrane during antiviral response.
- Yuki Hanada
- Naotada Ishihara
- Masatoshi Nomura
ArticleOpen Access11 Nov 2020 Nature Communications

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