Immunological Reviews最新文献

Vγ9Vδ2 T-cells are universally present in humans and represent one of the most prevalent TCR reactivities, evolutionarily conserved across diverse mammalian species. They are an innate-like subset featuring a semi-invariant TCR repertoire that drives their well-recognized reactivity to small, non-peptidic phosphoantigens (pAg). Crucially, they can distinguish between highly immunostimulatory microbially derived pAg and much less potent host-derived pAg, with the former effectively acting as a pathogen associated molecular pattern (PAMP) and the Vγ9Vδ2 TCR as a surrogate pattern recognition receptor (PRR). Ample evidence supports important Vγ9Vδ2-mediated contributions to immunity against diverse pathogenic bacteria and parasites, mediated by their potent effector and immunoregulatory functions. The molecular basis of the pAg sensing mechanism underpinning such responses has, however, remained highly mysterious. Despite this, past studies have established that pAg sensing is MHC-independent, extremely fast, exquisitely pAg-sensitive, and dependent upon target cell expression of key BTN-family molecules, notably BTN3A and BTN2A1. Here we contextualize these findings and several recent studies addressing pAg sensing. We integrate these into a single unified theory of pAg sensing interpretable from different perspectives, both intracellular and extracellular, biophysical, and topological. We prioritize critical questions to address in the context of this proposed model. Finally, we suggest the model will provide a molecular template for antigen recognition by other related γδ T-cell subsets.

R. Nocerino, L. Carucci, S. Coppola, F. Oglio, A. Masino, A. Agizza, L. Paparo, R. Berni Canani, “The journey toward disease modification in cow milk protein allergy,” Immunological Reviews 326, no. 1 (2024): 191–202, https://doi.org/10.1111/imr.13372. Epub 2024 Jul 24. PMID: 39046826.

Correction of the Acknowledgement Section

With regards to the article in the September 2024 issue of the Journal, the authors wish to correct the Acknowledgement Section due to the lack of the CUP codes related to funding. The correction to the Acknowledgement Section does not affect the results or conclusions of the article. The authors regret the lack.

We apologize for this error.

Current Version:

This review was supported by funding from the National Recovery and Resilience Plan, European Union–Next Generation EU (On Foods–Research and Innovation Network on Food and NutritionSustainability, Safety and Security—Working on Foods; codePE0000003), and from the Italian Ministry of Health-HealthOperational Plan Trajectory 5-Line of action “Creation of an action program for the fight against malnutrition in all its forms and for the dissemination of the principles of the diet Mediterranean”(Mediterranean Diet for Human Health Lab “MeDiHealthLab”; code T5-AN- 07). The funders had no influence on the review. We thank our patients and their parents/caregivers for their enthusiastic participation and dedication to all our studies. We thank all physicians, nurses, technicians, and staff members for their support during the studies. Open access publishing facilitated by Università degli Studi di Napoli Federico II, as part of the Wiley-CRUI-CARE agreement.

Revised Version:

This review was supported by funding from the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3—Call for tender No. 341 of March 15 2022 of Italian Ministry of University and Research funded by the European Union—NextGenerationEU. Project code PE00000003, Concession Decree No. 1550 of October 11, 2022, adopted by the Italian Ministry of University and Research, CUP E63C22002030007, project title “ON Foods—Research and innovation network on food and nutrition Sustainability, Safety and Security—Working ON Foods” and from the Italian Ministry of Health-Health Operational Plan Trajectory 5-Line of action “Creation of an action program for the fight against malnutrition in all its forms and for the dissemination of the principles of the Mediterranean diet” (Mediterranean Diet for Human Health Lab, “MeDiHealthLab,” code T5-AN-07, CUP E63C22002570006). The funders had no influence on the review. Wethank our patients and their parents/caregivers for their enthusiastic participation and dedication to all our studies. We thank all physicians, nurses, technicians, and staff members for their support during the studies. Open access publ

Asthma, a chronic respiratory condition that has seen a dramatic rise in prevalence over the past few decades, now affects more than 300 million people globally and imposes a significant burden on healthcare systems. The key pathological features of asthma include inflammation, airway hyperresponsiveness, mucus cell metaplasia, smooth muscle hypertrophy, and subepithelial fibrosis. Cytokines released by lung epithelial cells, stromal cells, and immune cells during asthma are critical to pathological tissue remodeling in asthma. Over the past few decades, researchers have made great strides in understanding key cells involved in asthma and the cytokines that they produce. Epithelial cells as well as many adaptive and innate immune cells are activated by environmental signals to produce cytokines, namely, type 2 cytokines (IL-4, IL-5, IL-13), IFN-γ, IL-17, TGF-β, and multiple IL-6 family members. However, the precise mechanisms through which these cytokines contribute to airway remodeling remain elusive. Additionally, multiple cell types can produce the same cytokines, making it challenging to decipher how specific cell types and cytokines uniquely contribute to asthma pathogenesis. This review highlights recent advances and provides a comprehensive overview of the key cells involved in the production of cytokines and how these cytokines modulate airway remodeling in asthma.

Childhood is a multifactorial disease, and recent research highlights the influence of early-life microbial communities in shaping disease risk. This review explores the roles of the gut and respiratory microbiota in asthma development, emphasizing the importance of early microbial exposure. The gut microbiota has been particularly well studied, with certain taxa like Faecalibacterium and Bifidobacterium linked to asthma protection, whereas short-chain fatty acids produced by gut microbes support immune tolerance through the gut–lung axis. In contrast, the respiratory microbiota, though low in biomass, shows consistent associations between early bacterial colonization by Streptococcus, Moraxella, and Haemophilus and increased asthma risk. The review also addresses the emerging roles of the skin microbiota and environmental fungi in asthma, though findings remain inconsistent. Timing is a critical factor, with early-life disruptions, such as antibiotic use, potentially leading to increased asthma risk. Despite significant advances, there are still unresolved questions about the long-term consequences of early microbial perturbations, particularly regarding whether microbial dysbiosis is a cause or consequence of asthma. This review integrates current findings, highlighting the need for deeper investigation into cross-organ interactions and early microbial exposures to understand childhood asthma pathophysiology.

Asthma is one of the most prevalent and extensively studied chronic respiratory conditions, yet the heterogeneity of asthma remains biologically puzzling. Established factors like exogenous exposures and treatment adherence contribute to variability in asthma risk and clinical outcomes. It is also clear that the endogenous factors of genetics and immune system response patterns play key roles in asthma. Despite significant existing knowledge in the above, divergent clinical trajectories and outcomes are still observed, even among individuals with similar risk profiles, biomarkers, and optimal medical management. This suggests uncaptured biological interactions that contribute to asthma's heterogeneity, for which the role of host microbiota has lately attracted much research attention. This review will highlight recent evidence in this area, focusing on bedside-to-bench investigations that have leveraged omic technologies to uncover microbiome links to asthma outcomes and immunobiology. Studies centered on the respiratory system and the use of multi-omics are noted in particular. These represent a new generation of reverse-translational investigations revealing potential functional crosstalk in host microbiomes that may drive phenotypic heterogeneity in chronic diseases like asthma. Multi-omic data offer a wide lens into ecosystem interactions within a host. This informs new hypotheses and experimental work to elucidate mechanistic pathways for unresolved asthma endotypes. Further incorporation of multi-omics into patient-centered investigations can yield new insights that hopefully lead to even more precise, microbiome-informed strategies to reduce asthma burden.

W. L. Kan, C. M. Weekley, T. L. Nero, et al. “The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities,” Immunological Reviews 329 (2025): e13430, https://doi.org/10.1111/imr.13430.

In the article, there was an error in the funding grant in the Acknowledgment.

The second sentence reads:

Hercus and A.F. Lopez (APP1148221) and Leukemia & Lymphoma Society Chronic Myelomonocytic Leukemia Special Initiative to R. Majeti, D. Thomas, and A.F. Lopez (LLS 8042-24).

The sentence should read:

Hercus and A.F. Lopez (APP1148221) and the Leukemia & Lymphoma Society with support from the Mike & Sofia Segal Foundation to R. Majeti, D. Thomas, and A.F. Lopez (LLS 8042-24).

We apologize for this error.

It has long been appreciated that farm exposure early in life protects individuals from allergic asthma. Understanding what component(s) of this exposure is responsible for this protection is crucial to understanding allergic asthma pathogenesis and developing strategies to prevent or treat allergic asthma. In this review, we introduce the concept of Farm-Friends, or specific microbes associated with both a farm environment and protection from allergic asthma. We review the mechanism(s) by which these Farm-Friends suppress allergic inflammation, with a focus on the molecule(s) produced by these Farm-Friends. Finally, we discuss the relevance of Farm-Friend administration (oral vs. inhaled) for preventing the development and severity of allergic asthma throughout childhood and adulthood. By developing a fuller understanding of which Farm-Friends modulate host immunity, a greater wealth of prophylactic and therapeutic options becomes available to counter the current allergy epidemic.