Study of Interest: Landscape of Mast Cell Populations across Organs in Mice and Humans

Our team at the Toxicant-Induced Loss of Tolerance (TILT) Program at UT Health San Antonio wanted to share this important external study:

Landscape of Mast Cell Populations across Organs in Mice and Humans” from researchers at the Toulouse Institute for Infectious and Inflammatory Diseases with funding from the National Institute of Allergy and Infectious Diseases.

Mast cells (MCs) are distributed in virtually all organs and have been described as important cellular players in many pathological contexts, including allergy …
In aggregate, this study constitutes an online resource that regroups multiple MC [mast cells] single-cell transcriptomic profiles from various mouse and human organs and should help to refine MCs annotation and better understand their specialized functions across organs.

Based on these findings, one might anticipate far-reaching and widely varying effects when any toxicant(s) alters mast cells genetically or epigenetically, said Dr. Claudia Miller, allergist/immunologist, professor emeritus, and leader of the TILT Program at UT Health San Antonio.

What effects?

Multi-system symptoms plus new-onset intolerances for chemicals, foods and drugs, Miller said.

“The severity of symptoms and intolerances as well as their life impact are exactly what the internationally validated QEESI (Quick Environmental Exposure and Sensitivity Inventory) measures and what we have called ‘Toxicant-induced Loss of Tolerance,’ or TILT, for a quarter of a century,” Miller said. “The QEESI works as a measurement tool for the effects of toxicants on mast cells only because it was based upon the reports of affected groups of individuals who became ill following well-documented exposures to pesticides, VOCs during new construction or remodeling, breast implants, Gulf War chemicals and fires, etc.”

Miller and her team first proposed the mast cell alteration/sensitization biomechanism for TILT in a 2021 paper published in Environmental Sciences Europe.

Mast cells are considered the immune system’s “first responders.” They originate in the bone marrow and migrate to the interface between tissues and the external environment where they then reside. When exposed to “xenobiotics,” foreign substances like chemicals and viruses, they can release thousands of inflammatory molecules called mediators. This response results in allergic-like reactions, some very severe.

These cells can be sensitized by a single acute exposure to xenobiotics such as pesticides or solvents, or by repeated lower-level exposures, such as breathing volatile organic compounds (VOCs) associated with remodeling or new construction. Thereafter, even low levels of those and other unrelated substances can cause the mast cells to release the mediators that can lead to inflammation and illness.

Miller’s study found a close correlation between patients diagnosed with mast cell activation syndrome and mediator release (MCAS) and individuals reporting chemical intolerance via the 50-question QEESI survey.

As the likelihood of patients having MCAS increased, their likelihood of being chemically intolerant similarly increased, with nearly identical patterns of symptoms and intolerances. The close correspondence between MCAS and TILT patients suggests that environmental exposures disrupt mast cells, and may underlie both of these challenging conditions.

How chemically sensitive are you? Are you TILTed?

Answer these three questions from Hoffman TILT’s Brief Environmental Exposure and Sensitivity Inventory (BREESI):

  1. Do you feel sick when you are exposed to tobacco smoke, certain fragrances, nail polish/remover, engine exhaust, gasoline, air fresheners, pesticides, paint/thinner, fresh tar/asphalt, cleaning supplies, new carpet or furnishings? By sick, we mean: headache, difficulty thinking, difficulty breathing, weakness, dizziness, upset stomach, etc.
  2. Are you unable to tolerate or do you have adverse or allergic reactions to any drugs or medications (such as antibiotics, anesthetics, pain relievers, X-ray contrast dye, vaccines or birth control pills), or to an implant, prosthesis, contraceptive chemical or device, or other medical/surgical/dental material or procedure?
  3. Are you unable to tolerate or do you have adverse reactions to any foods such as dairy products, wheat, corn, eggs, caffeine, alcoholic beverages, or food additives (e.g., MSG, food dye)?

If you answer YES to any of these three questions, take the Quick Environmental Exposure and Sensitivity Inventory (QEESI) and share the results with your doctor!