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<p>Allergic diseases are common and affect a large proportion of the population. Interleukin-13 (IL-13)-expressing follicular helper T (T<sub>FH</sub>13) cells are a newly identified population of T<sub>FH</sub> cells that have been associated with high-affinity IgE responses. However, the origins, developmental signals, transcriptional programming and precise functions of T<sub>FH</sub>13 cells are unknown. Here, we examined the developmental signals for T<sub>FH</sub>13 cells and found a direct and progressive differentiation pathway marked by the production of IL-21. These two pathways differed in kinetics and extrinsic requirements. However, both pathways converged, forming transcriptionally similar T<sub>FH</sub>13 cells that express the transcription factor JunB as a critical stabilizing factor. Using an intersectional genetics-based T<sub>FH</sub>13-diphtheria toxin receptor model to perturb these cells, we found that T<sub>FH</sub>13 cells were essential to drive broad germinal center responses and allergen-specific IgG and IgE. Moreover, we found that IL-21 is a broad positive regulator of allergen germinal center B cells and synergizes with IL-13 produced by T<sub>FH</sub>13 cells to amplify allergic responses. Thus, T<sub>FH</sub>13 cells orchestrate multiple features of allergic inflammation.</p>

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Progressively differentiated TFH13 cells are stabilized by JunB to mediate allergen germinal center responses

  • 期刊论文

  • 发表日期：

    2025年1月31日

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  • Pragya Chandrakar,
  • Cody S. Nelson,
  • Manuel A. Podestà,
  • Cecilia B. Cavazzoni,
  • Maya Gempler,
  • Jeong-Mi Lee,
  • Sierra Richardson,
  • Hengcheng Zhang,
  • Snigdha Samarpita,
  • Maria Ciofani,
  • Talal Chatila,
  • Vijay K. Kuchroo,
  • Peter T. Sage

摘要

Allergic diseases are common and affect a large proportion of the population. Interleukin-13 (IL-13)-expressing follicular helper T (TFH13) cells are a newly identified population of TFH cells that have been associated with high-affinity IgE responses. However, the origins, developmental signals, transcriptional programming and precise functions of TFH13 cells are unknown. Here, we examined the developmental signals for TFH13 cells and found a direct and progressive differentiation pathway marked by the production of IL-21. These two pathways differed in kinetics and extrinsic requirements. However, both pathways converged, forming transcriptionally similar TFH13 cells that express the transcription factor JunB as a critical stabilizing factor. Using an intersectional genetics-based TFH13-diphtheria toxin receptor model to perturb these cells, we found that TFH13 cells were essential to drive broad germinal center responses and allergen-specific IgG and IgE. Moreover, we found that IL-21 is a broad positive regulator of allergen germinal center B cells and synergizes with IL-13 produced by TFH13 cells to amplify allergic responses. Thus, TFH13 cells orchestrate multiple features of allergic inflammation.