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Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity

Sudheendra Hebbar Subramanyam1, Judit Turyne Hriczko1, Angeliki Pappas1

  • 1Department of Pediatrics, RWTH Aachen University, Pauwelsstr 30, 52074, Aachen, Germany.

Scientific Reports
|March 7, 2023
PubMed

Insights

Tofacitinib effectively treats experimental colitis in mice when administered after symptom onset, but not when given preventatively. This JAK inhibitor ameliorates disease activity, though it does not prevent colitis occurrence.

Area of Science:

  • Immunology
  • Gastroenterology
  • Pharmacology

Background:

  • Ulcerative colitis is treated with tofacitinib, a Janus kinase (JAK) inhibitor.
  • Limited mechanistic data exist on tofacitinib's efficacy in experimental colitis models.

Purpose of the Study:

  • To investigate the effectiveness of tofacitinib in a murine model of T cell transfer-induced colitis.
  • To determine if tofacitinib prevents or treats experimental colitis.

Main Methods:

  • Experimental colitis was induced in RAG2-/- mice by transferring CD4+CD25- T cells.
  • Mice received tofacitinib (10 or 40 mg/kg) either immediately after T cell transfer or after disease onset.
  • Disease activity was assessed clinically and histologically.

Main Results:

  • Tofacitinib treatment initiated immediately after T cell transfer enhanced CD4+ T cell expansion and did not prevent colitis.
  • Treatment started after the onset of colitis symptoms ameliorated clinical and histological disease activity.
  • Tofacitinib demonstrated therapeutic efficacy in established experimental colitis but not as a preventative measure.

Conclusions:

  • Tofacitinib is effective in treating established murine experimental T cell transfer colitis.
  • Early intervention with tofacitinib does not prevent disease development and may enhance T cell expansion.

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