Xin Li, Ph.D.

Xin Li, Ph.D., is an Assistant Professor (tenure-track) in the Department of Pediatrics at UT Southwestern Medical Center, with a secondary appointment in the Department of Immunology. His research interests lie in studying host-microbiota interactions in health and disease. Using innovative techniques in microbiology and immunology, and multiple model organisms (bacteria, fungi, drosophila, mice, and humans), his research aims to investigate the fundamental mechanisms by which gut commensal bacteria and fungi regulate local and systemic inflammatory immune responses.

For his Ph.D., under the mentorship of Dr. Wendy Watford at the University of Georgia, Dr. Li studied the role of Tpl2, a host serine-threonine kinase, in modulating T regulatory and Th17 cell function, identifying a potential therapeutic target for autoimmune disorders. During his postdoctoral training at Weill Cornell Medical College, mentored by Dr. Iliyan Iliev and co-mentored by Dr. David Artis, he focused on the impact of gut commensal fungi on host immune responses. His recent work revealed that fungal sensing by tissue-resident CX3CR1+ mononuclear cells in the gut can influence distal allergic airway disease, with specific immune cells transmitting signals to the lungs, initiating early mechanistic studies for gut-lung immune crosstalk (Li et al., Cell Host and Microbe, 2018; Leonardi, Li et al., Science, 2018). In a recent study (Li et al., Nature, 2022), Dr. Li demonstrated the significance of microbial strain diversity in driving inflammatory immunity. By analyzing diverse fungal strains and their fungal factors, he found that high levels of the fungal candidalysin (a pore-forming toxin) were associated with more severe ulcerative colitis. Replicating these results in murine colitis models, Dr. Li identified a key pore-forming toxin (candidalysin) that mediates niche-specific inflammatory immunity. These findings highlight the importance of personalized approaches in developing microbiome-based therapeutics. In 2023, he joined the faculty at UT Southwestern in the Departments of Pediatrics and Immunology. Dr. Li and his team continue their work studying host-microbe interactions and tissue immunity using multiple model organisms.

His new research directions involve:

i) Identifying novel host factors involved in bacterial and fungal sensing to regulate inflammatory diseases.
ii) Identifying new microbial factors involved in bacterial and fungal sensing to regulate inflammatory diseases. These factors may include pore-forming toxins and other toxins.
iii) Identifying how microbe sensing of host-derived factors in the gut controls microbial commensalism and pathogenicity.
iv) Utilizing fungi as a model system, genetic engineering of microbial effectors to understand how a microbe dictates protective immunity, and pathogenic immunity at tissue barriers.

Contact: xin.li@utsouthwestern.edu 

Graduate School

University of Georgia (2016), Immunology

• Host-Microbe Interactions, Mucosal Immunology, Fungal Immunology, and Inflammatory Diseases
• Mucosal Immunology

Featured Publications

Immune regulation by fungal strain diversity in inflammatory bowel disease.

Li XV, Leonardi I, Putzel GG, Semon A, Fiers WD, Kusakabe T, Lin WY, Gao IH, Doron I, Gutierrez-Guerrero A, DeCelie MB, Carriche GM, Mesko M, Yang C, Naglik JR, Hube B, Scherl EJ, Iliev ID, Nature 2022 Mar 603 7902 672-678

Gut Mycobiota in Immunity and Inflammatory Disease.

Li XV, Leonardi I, Iliev ID, Immunity 2019 Jun 50 6 1365-1379

Response to Fungal Dysbiosis by Gut-Resident CX3CR1⁺ Mononuclear Phagocytes Aggravates Allergic Airway Disease.

Li X, Leonardi I, Semon A, Doron I, Gao IH, Putzel GG, Kim Y, Kabata H, Artis D, Fiers WD, Ramer-Tait AE, Iliev ID, Cell Host Microbe 2018 Dec 24 6 847-856.e4

CX3CR1⁺ mononuclear phagocytes control immunity to intestinal fungi.

Leonardi I, Li X, Semon A, Li D, Doron I, Putzel G, Bar A, Prieto D, Rescigno M, McGovern DPB, Pla J, Iliev ID, Science 2018 Jan 359 6372 232-236

Mucosal fungi promote gut barrier function and social behavior via Type 17 immunity.

Leonardi I, Gao IH, Lin WY, Allen M, Li XV, Fiers WD, De Celie MB, Putzel GG, Yantiss RK, Johncilla M, Colak D, Iliev ID, Cell 2022 Feb

Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome.

Jin WB, Li TT, Huo D, Qu S, Li XV, Arifuzzaman M, Lima SF, Shi HQ, Wang A, Putzel GG, Longman RS, Artis D, Guo CJ, Cell 2022 Jan

Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn's disease.

Doron I, Mesko M, Li XV, Kusakabe T, Leonardi I, Shaw DG, Fiers WD, Lin WY, Bialt-DeCelie M, Román E, Longman RS, Pla J, Wilson PC, Iliev ID, Nat Microbiol 2021 Dec 6 12 1493-1504

Human gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies.

Doron I, Leonardi I, Li XV, Fiers WD, Semon A, Bialt-DeCelie M, Migaud M, Gao IH, Lin WY, Kusakabe T, Puel A, Iliev ID, Cell 2021 Feb 184 4 1017-1031.e14

Macrophages Maintain Epithelium Integrity by Limiting Fungal Product Absorption.

Chikina AS, Nadalin F, Maurin M, San-Roman M, Thomas-Bonafos T, Li XV, Lameiras S, Baulande S, Henri S, Malissen B, Lacerda Mariano L, Barbazan J, Blander JM, Iliev ID, Matic Vignjevic D, Lennon-Duménil AM, Cell 2020 Oct 183 2 411-428.e16

Macrophage interactions with fungi and bacteria in inflammatory bowel disease.

Leonardi I, Li X, Iliev ID Curr. Opin. Gastroenterol. 2018 Nov 34 6 392-397

• NIH/NHLBI Pathway to Independence Award (K99/R00)
  (2023)
• Charles H. Revson Senior Postdoctoral Biomedical Fellowship
  (2019-2022)
• The American Association of Immunologists Careers in Immunology Fellowship
  (2015)

• Member, the American Association of Immunologists (2014)