@article{pmid41499395,

title = {T-bet-expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape},

author = {Eduard Ansaldo and Daniel Yong and Nathan Carrillo and Taryn McFadden and Mahnoor Abid and Dan Corral and Claudia Rivera and Taylor Farley and Nicolas Bouladoux and Inta Gribonika and Yasmine Belkaid},

doi = {10.1073/pnas.2520747122},

issn = {1091-6490},

year  = {2026},

date = {2026-01-01},

urldate = {2026-01-01},

journal = {Proc Natl Acad Sci U S A},

volume = {123},

number = {2},

pages = {e2520747122},

abstract = {Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption and barrier functions of this mucosal tissue. Despite the abundance of tissue resident activated T cells, their contributions to these various roles remain poorly understood. Here, we identify a dominant population of IL-10 producing, T-bet-expressing Tr1 T cells, residing in the small intestinal lamina propria at homeostasis. Remarkably, these intestinal Tr1 cells emerge at the time of weaning and accumulate independently of the microbiota displaying similar abundance, function, and TCR repertoire under germ-free conditions. Instead, the small intestinal T-bet Tr1 program is driven and shaped by dietary antigens, and accumulates in a cDC1-IL-27-dependent manner. Upon activation, these cells robustly express IL-10 and multiple inhibitory receptors, establishing a distinct suppressive profile. Altogether, this work uncovers a previously unappreciated dominant player in homeostatic small intestinal immunity with the potential to play critical suppressive roles in this tissue, raising important implications for the understanding of immune regulation in the intestine.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41428888,

title = {Maladaptive immunity to the microbiota promotes neuronal hyperinnervation and itch via IL-17A},

author = {Jeremie Delaleu and Veronica Burstein and Eduard Ansaldo and Ignacio Becaccece and Motoyoshi Nagai and Nicolas Bouladoux and Dan Corral and Andrea Muñoz Zamora and Adelle Ayash and Margery Smelkinson and Lilian Sun and Yasmine Belkaid and Michel Enamorado},

doi = {10.1073/pnas.2525146122},

issn = {1091-6490},

year  = {2025},

date = {2025-12-01},

urldate = {2025-12-01},

journal = {Proc Natl Acad Sci U S A},

volume = {122},

number = {52},

pages = {e2525146122},

abstract = {The interaction between the immune system and the somatosensory system plays a fundamental role in the regulation of diverse biological processes. Chronic itch is a common yet hard-to-treat symptom of many inflammatory skin conditions. One hallmark of chronic itch is the hyperinnervation of the skin by sensory fibers, yet what drives this aberrant nerve growth or how it contributes to disease progression remains unclear. Here, we identify IL-17A and immunity to skin microbiota as key triggers of sensory neuron plasticity and pruritus. In a murine model of psoriatic itch, we show that exposure to  prior to experimental psoriasis results in heightened skin inflammation, increased itch, and marked hyperinnervation of CGRPα sensory neurons. Accordingly, single-nuclei RNA sequencing of dorsal root ganglia reveals that microbiota-driven inflammation induces a regenerative transcriptional program in sensory neurons, including upregulation of axonal growth, injury response, and IL-17RA signaling pathways. Mechanistically, we show that IL-17A/IL-17RA signaling within TRPV1 sensory neurons drives hyperinnervation and pruritus, establishing a causal link between IL-17A and microbiota-driven immune responses in sensory circuit remodeling. Further, we identify sensory hyperinnervation as a key driver of chronic itch and inflammation. Collectively, we reveal that aberrant IL-17A signaling in sensory neurons, triggered by dysregulated microbiota immunity, promotes neuronal remodeling that amplifies itch and inflammation. These findings provide a framework for targeting microbiota-neuroimmune interactions as a therapeutic strategy for pruritus.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39954680,

title = {Mammary intraepithelial lymphocytes promote lactogenesis and offspring fitness},

author = {Dan Corral and Eduard Ansaldo and Jérémie Delaleu and Andrea C Pichler and Juraj Kabat and Cihan Oguz and Ana Teijeiro and Daniel Yong and Mahnoor Abid and Claudia A Rivera and Verena M Link and Katharine Yang and Liang Chi and Jia Nie and Olena Kamenyeva and Yiping Fan and Jerry Kok Yen Chan and Florent Ginhoux and Rémy Bosselut and Yasmine Belkaid},

doi = {10.1016/j.cell.2025.01.028},

issn = {1097-4172},

year  = {2025},

date = {2025-03-01},

urldate = {2025-03-01},

journal = {Cell},

volume = {188},

number = {6},

pages = {1662--1680.e24},

abstract = {Breastfeeding is an obligatory requirement of mammalian survival. This fundamental process is associated with the adaptation of maternal physiology, including the transformation of the mammary gland into a milk-secreting organ. How maternal immunity contributes to mammary gland remodeling and function remains largely unknown. Here, we show that maternal adaptive immunity plays a critical role in shaping lactogenesis. Specifically, physiological adaptation during pregnancy is associated with thymic involution and a paradoxical enrichment in intraepithelial lymphocyte (IEL) precursors that no longer migrate to the gut but instead preferentially accumulate within the mammary gland. IEL precursors differentiate into T-bet-expressing unconventional CD8αα lymphocytes in an IL-15-dependent manner. Mammary IELs control milk production by favoring the differentiation and maturation of contractile and milk-secreting cells, thereby promoting offspring fitness. Altogether, this work uncovers a contribution of the maternal adaptive immune system in organismal remodeling during pregnancy that is associated with mammary gland development and function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2480,

title = {Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis},

author = {Chi, L. and Liu, C. and Gribonika, I. and Gschwend, J. and Corral, D. and Han, S. J. and Lim, A. I. and Rivera, C. A. and Link, V. M. and Wells, A. C. and Bouladoux, N. and Collins, N. and Lima-Junior, D. S. and Enamorado, M. and Rehermann, B. and Laffont, S. and Guery, J. C. and Tussiwand, R. and Schneider, C. and Belkaid, Y.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/38574174},

doi = {10.1126/science.adk6200},

issn = {1095-9203 (Electronic) 0036-8075 (Linking)},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Science},

volume = {384},

number = {6692},

pages = {eadk6200},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38011570,

title = {Microbiota configuration determines nutritional immune optimization},

author = {Seong-Ji Han and Apollo Stacy and Dan Corral and Verena M Link and Mirian Krystel De Siqueira and Liang Chi and Ana Teijeiro and Daniel S Yong and P Juliana Perez-Chaparro and Nicolas Bouladoux and Ai Ing Lim and Michel Enamorado and Yasmine Belkaid and Nicholas Collins},

doi = {10.1073/pnas.2304905120},

issn = {1091-6490},

year  = {2023},

date = {2023-12-01},

urldate = {2023-12-01},

journal = {Proc Natl Acad Sci U S A},

volume = {120},

number = {49},

pages = {e2304905120},

abstract = {Mild or transient dietary restriction (DR) improves many aspects of health and aging. Emerging evidence from us and others has demonstrated that DR also optimizes the development and quality of immune responses. However, the factors and mechanisms involved remain to be elucidated. Here, we propose that DR-induced optimization of immunological memory requires a complex cascade of events involving memory T cells, the intestinal microbiota, and myeloid cells. Our findings suggest that DR enhances the ability of memory T cells to recruit and activate myeloid cells in the context of a secondary infection. Concomitantly, DR promotes the expansion of commensal Bifidobacteria within the large intestine, which produce the short-chain fatty acid acetate. Acetate conditioning of the myeloid compartment during DR enhances the capacity of these cells to kill pathogens. Enhanced host protection during DR is compromised when Bifidobacteria expansion is prevented, indicating that microbiota configuration and function play an important role in determining immune responsiveness to this dietary intervention. Altogether, our study supports the idea that DR induces both memory T cells and the gut microbiota to produce distinct factors that converge on myeloid cells to promote optimal pathogen control. These findings suggest that nutritional cues can promote adaptation and co-operation between multiple immune cells and the gut microbiota, which synergize to optimize immunity and protect the collective metaorganism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2430,

title = {ILC precursors differentiate into metabolically distinct ILC1-like cells during Mycobacterium tuberculosis infection},

author = {Corral, D. and Charton, A. and Krauss, M. Z. and Blanquart, E. and Levillain, F. and Lefrancais, E. and Sneperger, T. and Vahlas, Z. and Girard, J. P. and Eberl, G. and Poquet, Y. and Guery, J. C. and Arguello, R. J. and Belkaid, Y. and Mayer-Barber, K. D. and Hepworth, M. R. and Neyrolles, O. and Hudrisier, D.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35443177},

doi = {10.1016/j.celrep.2022.110715},

issn = {2211-1247 (Electronic)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Cell Rep},

volume = {39},

number = {3},

pages = {110715},

keywords = {},

pubstate = {published},

tppubtype = {article}

}