Modulation of the Immune System in Down Syndrome for Improved Outcomes and Neurodevelopment - 1

Inclusion Criteria: 1. Individuals with DS aged 6 years (inclusive) to 22 years (inclusive). All forms of DS will qualify, including complete trisomy 21, Robertsonian translocation trisomy 21, partial trisomy 21 (segmental duplication), and/or mosaic trisomy 21. 2. Available parent(s) or guardian(s) legally able to sign the consent form and who can complete study materials as appropriate. 3. Body weight is at least 10 kgs. Exclusion Criteria: 1. Prior treatment with a JAK inhibitor or with an investigational agent, device, or procedure within 21 days of enrollment. 2. Current or planned use of a JAK inhibitor during the 6-month study period. 3. Known allergies, hypersensitivity, or intolerance to tofacitinib. 4. Active, uncontrolled, or life-threatening infection that at the determination of the treating physician would preclude safe use of tofacitinib. 5. History of gastrointestinal perforation. 6. Vaccination with live attenuated virus within six weeks of inclusion in the study or planned during the study. Note on vaccines: Participants not yet vaccinated for MMR-V should consider their timeline for MMR-V vaccination. Specifically, the study team recommends MMR-V vaccination as soon as possible and delay study start until 6 weeks after MMR-V vaccinations. 7. Concomitant treatment with any of the following: 1. Concomitant treatment with other immunosuppressants (e.g., methotrexate, azathioprine, tacrolimus, cyclosporine). 2. Strong CYP3A4 inhibitors (e.g., ketoconazole). 3. Strong CYP3A4 Inducers (e.g., rifampin). 4. Moderate CYP3A4 inhibitor(s) with a strong CYP2C19 inhibitor(s) (e.g., fluconazole). 5. Other supplements or medications that at the determination of the treating physician would preclude safe use of tofacitinib. 8. Evidence of severe organ dysfunction, including severe renal impairment, that at the determination of the treating physician would preclude safe administration of tofacitinib. 9. Any history of leukemia, lymphoma, or unresolved transient myeloproliferative disorder. 10. Any current, recurrent, or metastatic forms of cancer. 11. Any cancer treatment within five years prior to study entry. 12. Known personal history of thrombosis or bleeding disorder. 13. History of tuberculosis, disseminated herpes zoster, disseminated herpes simplex, or recurrent localized herpes zoster. 14. Intravenous antimicrobial therapy within 3 months of inclusion in the study. 15. History of organ or bone marrow transplant. 16. History of myocardial infarction or stroke. 17. Evidence of lipid disorder, including but not limited to LDL \> 190 mg/dL, per discretion of the treating physician. 18. Participant received blood or plasma products within 30 days of the Baseline visit. 19. Treatment with intravenous immunoglobulin (IVIG) within 8 weeks of the Baseline visit. 20. Hospitalization longer than 6 months in the last year. 21. History of neurological syndrome that in the opinion of the study doctors would inhibit successful participation in the study. 22. Less than 6 weeks post-surgery at Baseline appointment. 23. Total vision or hearing loss (with no corrective devices available). 24. Participant must be able to attempt the neurodevelopment assessment battery at Baseline and caregiver must be able to complete proxy reports for neurodevelopmental assessments. 25. Poor venous access not allowing repeated blood tests or non-compliance with venipuncture requirements. 26. Participants may be excluded for other unforeseen reasons at the study doctor's discretion. 27. Pregnancy or breastfeeding. 28. Use of estrogen-containing oral contraceptives.