The Importance of Diversity in Immunology

Life on our planet relies on a global ecosystem composed of diverse, interdependent forces that must strike a harmonious balance. On an organismal level, immunologists have a deep appreciation for balanced integration of diversity, with disease resistance and our overall health depending on a complex orchestration of cells, physiologic pathways, and molecules that interface with every organ system. Indeed, deeper biological insights and rigorous inquiries into human health and disease rely on an open-minded synthesis of knowledge generated by scientists from around the world, without regard to their background, sexual orientation, religion, or ethnic group. Like distinct leukocyte populations that integrate signals from nonhematopoietic cell lineages to initiate or resolve inflammatory responses, the field of immunology routinely incorporates scientific advances from disparate fields, such as neurobiology, endocrinology, chemistry, engineering, and computer science, to overcome barriers to progress. In this way, scientific progress is inextricably linked to societal progress through recognition of different views, strategies, approaches, and innovative ideas of its constituents. We, therefore, must advocate actions that not only promote, but drive diversification of our laboratories, departments, institutions, and professional societies. These actions will invigorate not only our beloved field of immunology, but also the biomedical research enterprise as a whole.

Accordingly, we are proud to present a very special topical issue for The Journal of Immunology (The JI), entitled “Celebrating Diversity in Immunology,” that highlights an outstanding cadre of immunologists who have been recognized as current or future thought leaders given their considerable scientific accomplishments. For this issue, authors from diverse backgrounds, including different ethnicities, religions, ages, genders, sexual orientations, and physical abilities, were invited to contribute Brief Reviews on an immunology-related topic in which they have a deep expertise. Invited authors self-identified their background, and many have included a biographical statement addressing how their identity has shaped their science. We hope that this combined approach inspires progressive change and amplifies the call for enhancement of diversity to drive excellence in the field of immunology.

We welcome Co–Guest Editors De’Broski Herbert, Ph.D., and Irene Salinas, Ph.D. Herbert’s laboratory is focused on investigating the mechanisms of type 2 immunity and the resolution of chronic mucosal inflammation. Herbert earned his B.S. in microbiology from Xavier University and his Ph.D. in immunology from Thomas Jefferson Medical College. His thesis work demonstrated a critical role for IL-5, B-1 lymphocytes, and eosinophils in host-protective immunity against Strongyloides stercoralis. He also completed his postdoctoral work at the University of Cape Town in South Africa. Herbert has held independent investigator roles at Cincinnati Children’s Research Foundation and the University of California, San Francisco prior to the University of Pennsylvania. Salinas’s laboratory investigates the evolution of mucosal immune systems in vertebrates with a focus on host–microbiota interactions. She is a comparative immunologist, passionate about the use of nonmodel organisms to understand the diversity of immune systems on earth. Her recent work on fish nasal immunity also sparked an interest in neuroimmune communication in the olfactory–brain axis, which she investigates in the context of olfactory detection of viral pathogens. Salinas got her B.S. in marine biology in Alicante, Spain, and her M.Res. in applied fish biology at Plymouth University in the U.K. She then obtained her Ph.D. in cell biology from the University of Murcia in Spain. Salinas completed two postdoctoral fellowships at the University of Pennsylvania School of Veterinary Medicine and the National Institute of Water and Atmospheric Research in New Zealand.

We have compiled a total of 10 Brief Reviews for this special issue. The first, by Buckley and Dooley (1), showcases how diversification of Ag receptors in the immune systems of phylogenetically distinct species provides host protection against a veritable universe of constantly evolving pathogens. The authors highlight the importance of broad exploration in understanding mechanisms that facilitate pathogen detection and elimination. The second piece, written by Lee, Profant, and Wang (2), reviews the importance of sex bias in susceptibility to autoinflammatory disorders, especially via the influence of the CNS. They argue that the brain, its metabolic demands, and the immune cells contained within are each highly impacted by biological sex. Gibbs and Fairfax (3) then present us with an overview of how maternal parasitic infection can have lasting effects upon offspring immunity, including responses to vaccines. The authors highlight the critical importance of immunoregulatory networks in the mother on these effects through a comparison and contrast of parasites that invade the placenta to cause congenital infection versus extraplacental infections.

The three subsequent Brief Reviews focus on distinct organ systems that comprise skin and mucosal barrier tissues. Starting with skin immunity, Naik (4) reviews the astounding diversity of cutaneous immunity with regard to its cellular and soluble components. This review describes how hematopoietic, stromal, epithelial, and neuronal cell lineages in the skin respond in a delicately orchestrated manner to stave off infections and achieve homeostasis. Cairo and Webb (5) delve into the intestinal barrier with an emphasis on innate lymphoid populations, including NKT cells and innate lymphoid cells, which underscores how even minority populations can have a big impact in a large, complex environment. Clear parallels can be drawn between biology and societal issues in this regard. One may extrapolate transcendental principles in the importance of equality and inclusiveness in immunology, despite population size. Dowling and Forero (6) challenge our stereotypes of good and bad in their Brief Review titled “Beyond Good and Evil,” which reviews a duality in the protective and pathogenic roles of type I and III IFNs. Their review covers the deleterious consequences that result when IFN synthesis and IFN receptor signaling lack appropriate regulation. Of course, this topic is highly relevant amid the COVID-19 pandemic because IFN responses have been linked to much of the pathophysiology observed in severe COVID-19 patients.

In another good–evil balancing act, the Brief Review by Allen (7) focuses on the role of B cells in allergic responses, with a comprehensive overview of class-switch recombination, plasma cell differentiation, germinal center reactions, and processes that promote affinity maturation. A particular emphasis is placed on how B cells can both drive allergic disease through IgE, but also suppress allergy through IgG1 and regulatory B cell functions, highlighting how cell populations, much like human populations, can bear conflicting traits depending on their specific context. Carson, Gardner and Iweala (8) introduce us to the α-gal syndrome (AGS), an IgE-mediated hypersensitivity response to the glycan galactose-α-1,3-galactose (α-gal) found in red meat. α-gal is also a component of some pharmaceuticals and, therefore, individuals suffering from AGS can develop immediate hypersensitivity to such products. This syndrome is fascinating from an immunological perspective because it challenges several aspects of our current definition of IgE-mediated food allergies. AGS is a delayed (not immediate) hypersensitivity to a sugar (not peptide) Ag and is mediated by a tick bite (not by food consumption). In many ways, this review spotlights how immunology is all about diversity: immune responses always break molds!

In “Sweet Immune Checkpoint Targets to Enhance T Cell Therapy,” Derosiers, Aguilar, DeGaramo, and Posey (9) discuss another aspect of sugars in functional diversity. The authors focus on T cell–based immunotherapies, such as chimeric Ag receptor T cell therapy, and the dire need to overcome immune suppression for enhancing effectiveness against solid tumors. Genetic engineering approaches have the potential to solve checkpoint-mediated immune suppression and understanding the panoply of inhibitory glycan–lectin interactions is a critical step to improve cancer immunotherapeutics. We close with another area of intense research in posttranslational modifications (PTMs). In their Brief Review, Zangiabadi and Abdul-Sater (10) summarize the exciting field of PTMs on components of the NLRP3 inflammasome, a potent regulator of IL-1β cleavage and secretion that is implicated in many disease states. PTMs, such as ubiquitination, phosphorylation, sumoylation, and s-nitrosylation, establish a complex language for functional diversification and modulate the priming, activation, and intensity of the inflammasome response.

Our collection also includes a very special Immunology Notes and Resources article titled, “The Minority Scientists’ Experience: Challenging and Overcoming Barriers to Enhancing Diversity and Career Advancement” (11), which captures the essence of presentations and panel discussions sponsored by the American Association of Immunologists Minority Affairs Committee at IMMUNOLOGY2021™. This important session represented a call to action and provided strategies for enhancing diversity in our scientific community, dealing with microaggressions, and elevating mentorship for professional advancement.

We recognize that it is impossible to capture all aspects of diversity in a single collection, but we intend for this to be a starting point, highlighting how The JI is a welcoming home for authors of all backgrounds who continue to contribute significant advances in immunology. Our overarching hope is that this inaugural JI review series, which combines a rich diversity of immunological topics and investigators, will foster initiatives that are implemented to increase equity and inclusion in biomedical research. This special issue should reassure the future generation of immunologists across the globe that everyone belongs to immunology and that professional legitimacy can be achieved while staying true to oneself. Finally, let’s remember that this issue is but one starting point for the work that must be accomplished individually and collectively to end inequalities in all scientific fields.

De’Broski Herbert and Irene Salinas, Co–Guest Editors

Eugene M. Oltz, Editor-in-Chief