Rewriting the Rules of Skin Immunity: Discoveries to Revolutionize Vaccines, Inflammatory Disease, and Cancer Treatments
Dr. Inta Gribonika has a vivid imagination, cultivated from her childhood exploring the wilderness around her rural homeland in Latvia. Her grandmother’s traditional home remedies for skin ailments, derived from local plants, sparked in her a deep fascination with how the skin responds to its environment. Now in her laboratory at Lund University, she digs deep into this mystery. Exploring how the immune system operates in the skin, she has already made groundbreaking discoveries that upend long-held assumptions in the field. Her research could have a widespread impact on medicine, with important implications for vaccines, immune-mediated skin diseases, and cancer immunotherapies.
Skin is the body’s largest organ, forming the first line of defense against the external world. For decades, researchers studied small biopsies from this massive organ, missing crucial immune components found only in specific locations. Gribonika was not satisfied with the status quo; she had a larger vision. For a more comprehensive look at skin immunity, she examined whole mouse ears and discovered that B cells, thought to be absent, are present in small but important numbers. Located in specific immune clusters near hair follicles, called TLOs (tertiary lymphoid organs), they orchestrate critical antibody responses. “Once induced by microbiota, TLOs remain in the tissue indefinitely, contributing to continuous memory B cell and plasma cell output in the skin, production of highly protective systemic IgG responses, mucosal IgA antibodies, and release of immunoglobulins on the surface of the skin,” says Gribonika.
As a 2026 Michelson Prizes: Next Generation Grants recipient, she will examine how these TLOs work with the goal of leveraging this foundational knowledge for vaccine and immunotherapy advances. “The goal is to enhance immune protection at barrier surfaces to maintain health and eliminate pathogens before serious infection develops,” she says.
Vaccines that elicit immune protection at barrier surfaces like the skin, gut and lung have eluded scientists for decades. Current vaccines can only stimulate antibodies that circulate in the blood. “The challenge in vaccination has been inducing these tissue antibodies, which provide the crucial first line of defense at barrier surfaces,” says Gribonika. She hopes that by understanding these newly discovered immune structures in the skin and how they function, she can target them to drive local antibody production to finally achieve this holy grail in vaccinology.
This research could rewrite the rules of vaccine design, opening the door to vaccines delivered as creams or patches applied to the skin rather than injections. “Since TLOs form around hair follicles, these structures could serve as a ‘nature's needle’ that allow the vaccine molecules to penetrate and reach the TLO microenvironment,” says Gribonika. “Hair follicles have already been studied as delivery pathways for skin therapeutics in other fields.” These less invasive delivery methods could make vaccines easier to distribute and administer without the need for highly trained healthcare professionals, making them more accessible around the world.
Cracking the code for skin-targeted vaccines could also enable oral and inhaled vaccines, which target the gut and lungs respectively, as these barriers also have TLO-like structures that generate local immune responses. Applying these lessons across barrier tissues could generate a whole new class of TLO-targeted vaccines with the potential to transform global health by finally providing protection at the sites where pathogens first enter the body.
While TLOs contribute to normal immune processes and tissue health, they can also be found in various disease contexts. “TLOs are emerging as important players in skin inflammation and malignancies,” says Gribonika. Understanding their roles in disease could guide novel TLO-targeted immunotherapies that dial immune responses up or down depending on the context.
While TLO-targeted therapies could have a widespread impact across diverse fields of medicine, Gribonika warns that the approach will not be one size fits all and may even differ between men and women. “Systemic immune responses in lymph nodes, spleen, or blood don't differ much between sexes, but barrier tissue responses at the first interface with the outside world are dramatically different and controlled by androgens. Females have much greater potential to form TLOs,” she says. Gribonika aims to leverage this knowledge to better understand sex differences in vaccine efficacy and autoinflammatory disease incidence, and ultimately to turn these insights into precision therapies designed specifically for men and women.
Gribonika credits her mentors, Dr. Nils Lycke and Dr. Yasmine Belkaid, in fostering her creativity, allowing her to develop the innovative ideas that earned her the Michelson Prize. “I have been extremely fortunate to be supported, coached, molded, influenced and inspired by incredible mentors who cultivated freedom of thought and provided space for ‘out of the ordinary’ ideas.” Indeed, Gribonika embodies the spirit of the Michelson Prizes: Next Generation Grants, which are designed to support the bold imaginations of young scientists who challenge current dogma and apply disruptive concepts to drive transformational advances in medicine.
