Discovery immunology最新文献

[This corrects the article DOI: 10.1093/discim/kyae007.].

The study of immune phenotypes in wild animals is beset by numerous methodological challenges, with assessment of detailed aspects of phenotype difficult to impossible. This constrains the ability of disease ecologists and ecoimmunologists to describe immune variation and evaluate hypotheses explaining said variation. The development of simple approaches that allow characterization of immune variation across many populations and species would be a significant advance. Here we explore whether serum protein concentrations and coarse-grained white blood cell profiles, immune quantities that can easily be assayed in many species, can predict, and therefore serve as proxies for, lymphocyte composition properties. We do this in rewilded laboratory mice, which combine the benefits of immune phenotyping of lab mice with the natural context and immune variation found in the wild. We find that easily assayed immune quantities are largely ineffective as predictors of lymphocyte composition, either on their own or with other covariates. Immunoglobulin G (IgG) concentration and neutrophil-lymphocyte ratio show the most promise as indicators of other immune traits, but their explanatory power is limited. Our results prescribe caution in inferring immune phenotypes beyond what is directly measured, but they do also highlight some potential paths forward for the development of proxy measures employable by ecoimmunologists.

The immune system is crucial for defending organisms against pathogens and maintaining health. Traditionally, research in immunology has relied on laboratory animals to understand how the immune system works. However, there is increasing recognition that wild animals, due to their greater genetic diversity, lifespan, and environmental exposures, have much to contribute to basic and translational immunology. Unfortunately, logistical challenges associated with collecting and storing samples from wildlife, and the lack of commercially available species-specific reagents have hindered the advancement of immunological research on wild species. Extracellular vesicles (EVs) are cell-derived nanoparticles present in all body fluids and tissues of organisms spanning from bacteria to mammals. Human and lab animal studies indicate that EVs are involved in a range of immunological processes, and recent work shows that EVs may play similar roles in diverse wildlife species. Thus, EVs can expand the toolbox available for wild immunology research, helping to overcome some of the challenges associated with this work. In this paper, we explore the potential application of EVs to wild immunology. First, we review current understanding of EV biology across diverse organisms. Next, we discuss key insights into the immune system gained from research on EVs in human and laboratory animal models and highlight emerging evidence from wild species. Finally, we identify research themes in wild immunology that can immediately benefit from the study of EVs and describe practical considerations for using EVs in wildlife research.

Immune responses are widely accepted to be under circadian regulation via a molecular clock, with many practical consequences, but much less is known of how other biological rhythms could affect the immune system. In this study, we search for lunar rhythms (circalunar, circasemilunar, and circatidal cycles) in the immune expression of the recently marine-derived freshwater fish, the low-plate morph of the three-spined stickleback. We employed time series of immune expression (mRNA) measurements for 14 immune-associated genes, representing a variety of immunological pathways. Times series measurements were taken on fish populations in the wild, in seminatural outdoor mesocosms, and in the laboratory, according to sampling regimens originally designed to study circannual variation but with the additional potential to provide information about lunar variation. Our evidence best supported the existence of a very small endogenous tidal rhythm. This is consistent with previous suggestions of the existence of a primordial tidal endogenous clock, some elements of which may be conserved in animals evolving outside the marine environment.

Direct interaction between T-cells exerts a major influence on tissue immunity and inflammation across multiple body sites including the human gut, which is highly enriched in 'unconventional' lymphocytes such as γδ T-cells. We previously reported that microbial activation of human Vγ9/Vδ2⁺ γδ T-cells in the presence of the mucosal damage-associated cytokine IL-15 confers the ability to promote epithelial barrier defence, specifically via induction of IL-22 expression in conventional CD4⁺ T-cells. In the current report, we assessed whether other cytokines enriched in the gut milieu also functionally influence microbe-responsive Vγ9/Vδ2 T-cells. When cultured in the presence of IL-21, Vγ9/Vδ2 T-cells acquired the ability to induce expression of the immunoregulatory cytokine IL-10 in both naïve and memory CD4⁺ T-cells, at levels surpassing those induced by monocytes or monocyte-derived DCs. These findings identify an unexpected influence of IL-21 on Vγ9/Vδ2 T-cell modulation of CD4⁺ T-cell responses. Further analyses suggested a possible role for CD30L and/or CD40L reverse signalling in mediating IL-10 induction by IL-21 conditioned Vγ9/Vδ2 T-cells. Our findings indicate that the local microenvironment exerts a profound influence on Vγ9/Vδ2 T-cell responses to microbial challenge, leading to induction of distinct functional profiles among CD4⁺ T-cells that may influence inflammatory events at mucosal surfaces. Targeting these novel pathways may offer therapeutic benefit in disorders such as inflammatory bowel disease.

Despite extensive regulatory T cell (Treg) research, fundamental questions on in vivo dynamics remain to be answered. The current study aims to dissect several interwoven concepts in Treg biology, highlighting the 'self-reactivity' of Treg and their counterparts, namely naturally-arising memory-phenotype T-cells, as a key mechanism to be exploited by a human retroviral infection. We propose the novel key concept, Periodic T cell receptor (TCR)-signalled T-cells, capturing self-reactivity in a quantifiable manner using the Nr4a3-Timer-of-cell-kinetics-and-activity (Tocky) technology. Periodic and brief TCR signals in self-reactive T-cells contrast with acute TCR signals during inflammation. Thus, we propose a new two-axis model for T-cell activation by the two types of TCR signals or antigen recognition, elucidating how Foxp3 expression and acute TCR signals actively regulate Periodic TCR-signalled T-cells. Next, we highlight an underappreciated branch of immunological research on Human T-cell Leukemia Virus type 1 (HTLV-1) that precedes Treg studies, illuminating the missing link between the viral infection, CD25, and Foxp3. Based on evidence by single-cell analysis, we show how the viral infection exploits the regulatory mechanisms for T-cell activation and suggests a potential role of periodic TCR signalling in infection and malignant transformation. In conclusion, the new perspectives and models in this study provide a working framework for investigating Treg within the self-reactive T-cell spectrum, expected to advance understanding of HTLV-1 infection, cancer, and immunotherapy strategies for these conditions.