Reviews & Analysis

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  • This Review considers how the biophysical properties of a tissue are able to shape immune cell function through the process of mechanotransduction. There are multiple mechanotransduction pathways that operate in immune cells and the authors highlight these and the emerging field of mechanoimmunology.

    • Huixun Du
    • Juliet M. Bartleson
    • Manish J. Butte
    Review Article
  • There are many reasons why the development of a potent and durable vaccine to HIV-1 is exceptionally challenging, including the large genetic diversity of the virus and its complex mechanisms of immune evasion. In this Review, Haynes et al. discuss strategies for the induction of potent broadly neutralizing antibodies for HIV-1 and the steps that may be necessary for ultimate success.

    • Barton F. Haynes
    • Kevin Wiehe
    • George M. Shaw
    Review Article
  • Here, the authors consider our emerging understanding of COVID-19-associated coagulopathy. They focus on the complex interactions between innate immune, coagulation and fibrinolytic pathways that can lead to potentially life-threatening thrombosis following SARS-CoV-2 infection.

    • Edward M. Conway
    • Nigel Mackman
    • James H. Morrissey
  • Extracellular vesicles (EVs) are increasingly recognized as having ubiquitous roles in the immune system. This Review focuses on the progress made in the field in the past 5 years, including the roles of EVs in innate and adaptive immunity and their potential use in diagnosis and therapy.

    • Edit I. Buzas
    Review Article
  • Lorenzo Galluzzi and colleagues discuss the molecular mechanisms through which mitochondrial dysfunction elicits inflammatory reactions, the cellular pathways that are in place to control them and how the dysregulation of these systems contributes to pathology.

    • Saverio Marchi
    • Emma Guilbaud
    • Lorenzo Galluzzi
    Review Article
  • In this Review, Gorbunova and colleagues discuss the links between DNA damage, inflammation and ageing. They focus on the implications for premature ageing syndromes and multiple age-related diseases, and highlight potential therapeutic targets.

    • Yang Zhao
    • Matthew Simon
    • Vera Gorbunova
    Review Article
  • IL-17 cytokines drive biological responses that protect the host against many infections but can also contribute to host pathology in the context of infection and autoimmunity. Here, Kingston Mills highlights the different cellular sources of IL-17 and compares the pathological versus protective functions of these cytokines.

    • Kingston H. G. Mills
    Review Article
  • In early 2022, staff from the NIAID at the NIH organized a workshop focusing on the innate immune response to SARS-CoV-2. In this Viewpoint article, some of the organizers and invited speakers share their thoughts on key outcomes of this meeting.

    • Michael S. Diamond
    • John D. Lambris
    • John S. Tsang
  • Myeloid cells contribute to the immunosuppressive tumour microenvironment and can be responsible for resistance to cancer immunotherapy. Here, the authors describe the current therapies that aim to modulate the functional activities of myeloid cell populations, impacting their recruitment, survival and activity in the tumour microenvironment, acting at the level of cell surface receptors, signalling pathways, epigenetic machinery and metabolic regulators.

    • Sangeeta Goswami
    • Swetha Anandhan
    • Padmanee Sharma
    Review Article
  • In this Perspective, the authors reflect on the historical development of host-directed immunotherapeutic interventions for viral and bacterial infections, and then focus on how historical insights can be applied to current approaches to therapy of SARS-CoV-2 and Mycobacterium tuberculosis infections.

    • Robert S. Wallis
    • Anne O’Garra
    • Andreas Wack
  • The cytokine thymic stromal lymphopoietin (TSLP) has pleiotropic functions beyond allergic diseases and T helper 2-type immune responses. Here, the authors highlight the roles of TSLP — beneficial or deleterious — in infectious disease, chronic inflammatory disease and cancer by acting on many different cell types.

    • Risa Ebina-Shibuya
    • Warren J. Leonard
    Review Article
  • This Review explains how natural killer (NK) cells promote immunity to tumours. The authors cover the therapeutic approaches that are being developed to mobilize NK cells in patients with cancer, including NK cell activators, checkpoint blockade, cellular therapies, and bispecific and trispecific NK cell activating antibodies.

    • Natalie K. Wolf
    • Djem U. Kissiov
    • David H. Raulet
    Review Article
  • Mast cells are complex immune cells with varied functions. This Perspective explores the divergent phenotypes and functions of mast cells resulting from both their hard-wired ‘nature’ defined by their ontogeny and the ‘nurture’ they receive within specialized tissue microenvironments.

    • Ashley L. St. John
    • Abhay P. S. Rathore
    • Florent Ginhoux
  • Patients with autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, have distinct gut microbiota compositions compared to healthy controls. This Review explores how the gut microbiota influence autoimmune responses in extra-intestinal autoimmune diseases and discusses potential preventative and therapeutic strategies targeted at the microbiota–immune interface.

    • Eiji Miyauchi
    • Chikako Shimokawa
    • Hiroshi Ohno
    Review Article
  • Improving on current cancer immunotherapies will require engaging immune effectors beyond T cells alone. Predator–prey theory can reveal understudied and counterintuitive facets of antitumour immunity, inspiring new approaches to manipulate the tumour ecosystem in favour of cancer cell extinction.

    • Phineas T. Hamilton
    • Bradley R. Anholt
    • Brad H. Nelson
  • This Review explores the complex roles of immune cells in the onset and progression of multiple sclerosis, describing the influence of environmental and genetic factors on immune cell phenotype and function. The authors highlight that teasing out the precise roles of different immune cell subsets at different stages of the disease will be key to effective treatment strategies.

    • Kathrine E. Attfield
    • Lise Torp Jensen
    • Lars Fugger
    Review Article
  • This ‘guide to’ article provides an overview of the antigen processing and presentation pathways, which lead to the loading of antigenic peptides on major histocompatibility complex (MHC) molecules for detection by T cells.

    • Novalia Pishesha
    • Thibault J. Harmand
    • Hidde L. Ploegh
    Review Article
  • The cell-autonomous innate immune system has long been considered an evolutionary innovation of metazoans; however, recent evidence challenges this dogma. This Perspective describes the components of antiviral immunity that are conserved from bacteria to humans, and presents potential evolutionary scenarios to explain the observed conservation.

    • Tanita Wein
    • Rotem Sorek
  • Type 2 innate lymphoid cells (ILC2s) have diverse phenotypes across different tissues and disease states. Recent insights into ILC2 biology raise new possibilities for the improved treatment of cancer and of metabolic, infectious and chronic inflammatory diseases.

    • Hergen Spits
    • Jenny Mjösberg
    Review Article