The Gaffen Laboratory - Research & Publications

Research & Publications

General Background

The immune system strikes a remarkably tight balance between controlling infections while still limiting immunity to self tissues (autoimmunity). A case in point is T cell derived cytokines: while critical for protecting against infectious diseases, particularly fungal infections, they are also central to driving pathology in most autoimmune conditions. Consequently, ‘biologic’ drugs that neutralize cytokines or other immune molecules have become mainstays of treating autoimmune diseases.

The Gaffen lab takes a basic science approach to understand the molecular and cellular mechanisms that underline cytokine-mediated inflammation, whether for good (prevent infections) or bad (promote autoimmune pathology). Our main focus is IL-17, which is produced mainly by T cells and other lymphocytes.

IL-17 Signal Transduction

IL-17 acts mainly on stromal and epithelial cells, and hence links the immune system with inflamed tissues. IL-17 and its receptor are unique in structure and sequence from other known cytokine families, and the Gaffen lab was among the first to study the molecular signaling mechanisms induced by this novel family of cytokines. Efforts to understand this pathway in depth are a major focus of the lab.

Dr. Gaffen’s group was the first to demonstrate that IL-17 is critical for immunity to mucosal fungal infection, which we examined in the context of periodontal bone loss and a common commensal fungus, Candida albicans. Although normally not a problem in healthy individuals, C. albicans is the causative agent of mucosal thrush in the oral and vaginal tracts, and is also a serious hospital-acquired form of candidiasis that can be associated with >50% mortality. Our laboratory is interested in understanding how IL-17 coordinates immunity to C. albicans across tissues.

Antibodies that neutralize IL-17 were approved more than 10 years ago to treat psoriasis and other autoimmune or immunopathological diseases. Dr. Gaffen’s lab aims to understand the physiological impact of cytokine blockade, as well as the ways in which cytokine signaling might be exploited for therapeutic benefit.

Review by Li, Vyas et al. Science Immunology 2026

https://www.science.org/eprint/F5PGJ6YE47KKEUUVZBQR/full?activationRedirect=/doi/full/10.1126/sciimmunol.adq6406

Current Funding

Gaffen, Principal Investigator

R37-DE022550 – “Host and fungal regulation of Type 17 immunity to oral candidiasis” 2017-27

R01- AI162616 “RNA binding proteins in end-organ autoimmunity” 2022-27

Medical Research Grant “Arid5a – A novel biomarker and molecular driver of autoimmune arthritis” 2025-27

Gaffen, Co-Investigator

R01-DE031382 (PI, Marc Swidergall, UCLA/Lundquist Inst) “Oral commensal fungi and structural immunity” 2022-27

R01-AI079178 (PI, T Lu Cornell) “Lymphatic regulation of lymph node function in lupus” 2022-27

Selected Publications

Click here for all publications

Review Articles

Li X., Bechara R, Zhao J, McGeachy MJ, Gaffen SL. IL-17 receptor-based signaling and implications for disease. Nature Immunology 2019; 20:1594. https://www.nature.com/articles/s41590-019-0514-y

Gaffen SL, Moutsopoulos N. Regulation of Host-Microbe Interactions at Oral Mucosal Barriers by Type 17 Immunity. Science Immunology 2020; 5:eaau4594. https://immunology.sciencemag.org/content/5/43/eaau4594

Bechara R, Gaffen SL. ‘(m6)A’ stands for autommunity: Reading, writing and erasing RNA modifications during inflamation. Trends Immunol 2021; 42:1073 https://pubmed.ncbi.nlm.nih.gov/34728144/

Li Y, Vyas S, Draber P, Bechara R, Gaffen SL. The tissue-specific regulation of immunobiology by IL-17 signaling. Science Immunology, 2026; 11:eadq6406. https://www.science.org/eprint/F5PGJ6YE47KKEUUVZBQR/full?activationRedirect=/doi/full/10.1126/sciimmunol.adq6406

Fungal Immunity and IL-17/TH17 Cells

Coleman BM¶, Cook ME¶, Khan MR, Vogel AK, Wells AJ, Miao J, Vyas SP, Taylor TC, Aggor FEY, Ponde NO, Day I, Zou H, Peters BM, Gaffen SL. An estrogen-independent and IL-1-dependent pathway controls vulvovaginal candidiasis through combined IL-17/IL-22 signaling. PLoS Pathogens, 2026; 22:e1014202. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014202

Aggor FEY, Bertolinna M, Coleman BM, Ponde NO, Filler SG, Gaffen SL. Combinatorial actions of IL-22 and IL-17 drive optimal immunity to oral candidiasis through SPRRs. PLoS Pathogens,2024; 20(7):e1012302. https://pubmed.ncbi.nlm.nih.gov/38949991/

Taylor TC, Coleman BM, Arunkumar S, Dey I, Dillon JT, Ponde NO, Poholek AC, Schwartz DM, McGeachy MJ Conti HR, Gaffen SL. IkappaBzeta is an essential mediator of immunity to oropharyngeal candidiasis. Cell Host Microbe, 2023; 31:1700-13 https://pubmed.ncbi.nlm.nih.gov/37725983/

Aggor FEY, Break TJ, Trevejo-Nunez G, Whibley N, Coleman BM, Bailey RD, Kaplan DH, Naglik JR, Shan W, Shetty AC, McCracken C, Durum SK, Biswas PS, Bruno VM, Kolls JK, Lionakis MS, Gaffen SL. Oral epithelial IL-22/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis. Science Immunology, 2020; 5:eaba0570. https://immunology.sciencemag.org/content/5/48/eaba0570.long

Conti HR, Bruno VM, Childs EC, Daugherty S, Hunter JP, Mengesha BG, Saevig DL, Hendricks MR, Coleman BM, Brane L, Solis N, Cruz JA, Verma AH, Garg AV, Hise AG, Richardson JP, Naglik JR, Filler SG, Kolls JK, Sinha S, Gaffen SL. IL-17RA signaling in oral epithelium is critical for protection against oropharyngeal candidiasis. Cell Host & Microbe, 2016; 20:606-617. https://www.ncbi.nlm.nih.gov/pubmed/27923704

*** Note, mice available from The Jackson Laboratory https://www.jax.org/strain/034382

Verma AH, Richardson JP, Moyes DL, Ho J, Huppler AR, Ramani K, Coleman BM, Kane LP, Biswas PS, Hube B, Naglik JR, Gaffen SL. Oral epithelial cells orchestrate innate Type 17 responses to Candida albicans through the virulence factor Candidalysin. Science Immunology, 2017; 2:eaam8834.
https://www.ncbi.nlm.nih.gov/pubmed/29101209
https://www.ncbi.nlm.nih.gov/pubmed/29101210

Conti HR, Shen F, Nayyar N, Stocum E, Sun JN, Lindemann MJ, Ho AW, Hai JH, Yu JJ, Jung JW, Filler SG, Masso-Welch P, Edgerton M, Gaffen SL. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med, 2009; 206:299-311 (designated JEM Legacy paper)
https://www.ncbi.nlm.nih.gov/pubmed/19204111
https://www.ncbi.nlm.nih.gov/pubmed/19204107

Autoimmunity and Anti-cytokine Drugs

Li Y, Dey I, Vyas SP, Synackova A, Li D, Lubberts E, Ascherman DP, Draber P, Gaffen SL. TNF signaling in rheumatoid arthritis is mediated by the RNA binding protein Arid5a. JCI Insight, 2026; 11:e196411 https://insight.jci.org/articles/view/196411

Dey I, Li Y, Taylor TC, Peroumal D, Biswas PS, Sterneck E, Gaffen SL. C/EBPdelta mediates immunity to renal autoinflammatory disorders in a stage-specific manner. J Immunol, 2024, 213:767-778 https://academic.oup.com/jimmunol/article-abstract/213/6/767/7925931?redirectedFrom=fulltext

Shen F, Verma AH, Volk A, Jones B, Coleman BM, Loza M, Malaviya R, Elloso M, Gaffen SL*, Ort T*. Combined blockade of TNFα and IL-17A alleviates progression of collagen-induced arthritis without causing serious infections in mice. 2019; J Immunol, 202:2017-2026.
https://www.ncbi.nlm.nih.gov/pubmed/30745461

Monin L, Gudjonsson JE, Childs EE, Amatya N, Xing X, Verma AV, Coleman BM, Killeen M, Mathers A, Ward NL, Gaffen SL. MCPIP1/Regnase-1 restricts IL-17A- and IL-17C-dependent skin inflammation. J Immunol, 2017; 198:767-775.
https://www.ncbi.nlm.nih.gov/pubmed/27920272

Mechanisms of IL-17 Receptor Signaling

Li Y, Vyas SP, Mehta I, Asada N, Dey I, Taylor TC, Bechara R, Amatya N, Aggor FEY, Coleman BM, Li D, Yamamoto K, Ezenwa O, Sun Y, Sterneck E, McManus CJ, Panzer U, Biswas PS, Savan R, Das J, Gaffen SL*. The RNA binding protein Arid5a drives IL-17-dependent autoantibody-induced glomerulonephritis. J Exp. Med, 2024; 221:e20240656.

https://pubmed.ncbi.nlm.nih.gov/39058386/

Bechara R, Amatya N, Bailey RD, Li Y, Aggor FEY, Li D, Jawale C, Coleman BM, Dai N, Gokhale NS, Taylor TC, Horner SM, Poholek AC, Bansal A, Biswas PS, Gaffen SL. The m6A reader IMP2 directs autoimmune inflammatoin through an IL-17- and TNFalpha-dependent C/EBP transcription factor axis. Science Immunology, 2021; 6:eabd1287. http://immunology.sciencemag.org/cgi/content/full/6/61/eabd1287?ijkey=Ar2nw4ClbBkV2&keytype=ref&siteid=immunology

Amatya N, Childs EE, Cruz JA, Aggor FEY, Garg AV, Berman AJ, Gudjonsson JE, Atasoy U, Gaffen SL. IL-17 integrates multiple self-reinforcing, feed-forward mechanisms through the RNA-binding protein Arid5a. Science Signaling, 2018; 11:eaat4617.
http://stke.sciencemag.org/content/sigtrans/11/551/eaat4617.full.pdf?ijkey=9t7OnA3f2T2QU&keytype=ref&siteid=sigtrans

Garg AV, Amatya N, Chen K, Cruz JA, Grover P, Whibley N, Conti HR, Mir GH, Sirakova T, Childs EC, Smithgall TE, Biswas PS, Kolls JK, McGeachy MJ, Kollatukudy PE, Gaffen SL. MCPIP1* endoribonuclease activity negatively regulates interleukin-17-mediated signaling and inflammation. Immunity, 2015; 43:475-487.
https://www.ncbi.nlm.nih.gov/pubmed/26320658

*MCPIP1=Regnase-1 or Zc3h12a