In a groundbreaking study published in Nature Microbiology, researchers have provided fresh insights into the innate immune defenses of the small intestine that combat infections by Vibrio cholerae, the bacterium responsible for the life-threatening diarrheal disease cholera. Despite being a major global health threat with periodic outbreaks causing significant mortality, the detailed mechanisms by which the small intestinal mucosa resists V. cholerae have remained largely elusive. This innovative investigation utilized cutting-edge single-cell RNA sequencing (scRNA-seq) technology to dissect the complex interplay between epithelial cells and immune populations in the infant mouse small intestine during infection, revealing an intricate cellular response that could pave the way to new therapeutic strategies.

The study begins by characterizing changes in gene expression within individual cell types in the small intestine following V. cholerae infection. This high-resolution approach permitted the identification of a distinct subset of enterocytes—intestinal epithelial cells—showing marked upregulation of genes associated with host defense functions. Such specialization suggests the presence of dedicated epithelial cells primed to counteract bacterial invasion. Interestingly, these defense-associated enterocytes expanded in abundance during infection, underscoring a dynamic epithelial response to microbial challenge rather than a static barrier.

A pivotal discovery was the source and role of the cytokine interleukin-22 (IL-22), a known regulator of epithelial integrity. The team found that during infection, IL-22 production rose significantly, emanating primarily from group 3 innate lymphoid cells (ILC3s). These cells serve as sentinels within the gut mucosa, rapidly responding to pathogen encounter by secreting cytokines that shape epithelial function and barrier health. The IL-22 surge appeared to orchestrate a mucosal defense program, strengthening the epithelial front lines against V. cholerae colonization.

To better understand the therapeutic potential of IL-22, researchers administered a recombinant IL-22 fused with an immunoglobulin Fc region (IL-22Fc) prophylactically to mice before V. cholerae exposure. This intervention triggered enhanced production of Reg3β, an antimicrobial peptide with potent vibriocidal activity, from enterocytes. The data suggested that IL-22Fc treatment directly augmented the innate antimicrobial arsenal of the small intestine epithelium, thereby limiting bacterial growth and infection severity.

Beyond antimicrobial peptides, IL-22Fc profoundly affected the differentiation and abundance of secretory cell lineages within the small intestine. Specifically, there was a notable increase in the numbers of goblet cells capable of producing Muc2, a key mucus component in the gut. This mucus was secreted into the intestinal crypts—glandular niches critical for epithelial regeneration—resulting in a protective mucus barrier that hampered V. cholerae’s ability to adhere to the epithelial surface. This mucus-mediated physical barrier likely represents a crucial first line of defense impeding bacterial colonization and subsequent invasion.

The protective capacity of IL-22–mediated responses was strikingly evident at the physiological level. Mice treated with IL-22Fc showed significantly reduced bacterial colonization of their intestines, translating into protection from severe diarrhea and death, hallmark manifestations of cholera infection. These findings not only highlight the importance of epithelial defenses in gut immunity but also position IL-22 as a potential mucosal immunotherapeutic target to protect vulnerable populations from cholera.

This study also enriches the understanding of enterocyte specialization, demonstrating that certain epithelial cell subsets can reprogram their functions toward host defense upon challenge. Such plasticity was previously underappreciated in the field but emerges as essential to maintaining mucosal homeostasis during bacterial infection. The ability of the intestinal epithelium to dynamically shift towards a defensive phenotype likely reflects evolutionary pressures to balance nutrient absorption with pathogen resistance.

Moreover, the integrated single-cell transcriptome profiling illuminated the complex cellular ecosystem of the small intestine, where immune and epithelial cells engage in a finely tuned dialogue. Group 3 innate lymphoid cells, traditionally recognized for their roles in mucosal immunity, were validated as major sources of IL-22, positioning them centrally in coordinating epithelial responses. This cross-talk exemplifies how mucosal immunity relies on both cell-intrinsic and paracrine signaling pathways to mount effective, localized protection.

From a translational perspective, the therapeutic application of IL-22Fc opens a novel avenue to bolster gut barrier defenses. The fusion protein format extends the half-life and bioavailability of IL-22, overcoming limitations of endogenous cytokine instability. This strategy could form the basis for innovative prophylactic interventions, especially in endemic regions where cholera outbreaks pose recurrent threats to public health.

The study further sheds light on the molecular cues driving goblet cell expansion and mucus secretion in response to IL-22 signaling. Muc2 upregulation and mucus secretion serve as critical components of the epithelial shield, entrapping pathogens and limiting their epithelial interactions. Understanding how these differentiation pathways are regulated invites future research to harness or mimic such mechanisms for enhanced mucosal protection across diverse infectious diseases.

Importantly, this research also provides a model for exploring epithelial and immune cell dynamics in other enteric infections. By applying single-cell technologies, scientists can unveil cellular heterogeneity and uncover specialized subsets involved in disease resistance or pathogenesis. Such insights will fuel precision medicine approaches tailored to reinforce mucosal barriers and modulate immune responses at the gut interface.

In conclusion, the findings from this pivotal study redefine the role of IL-22 and its mediated pathways in shaping the small intestinal mucosal defense against Vibrio cholerae. Through the emergence of specialized, defense-equipped enterocytes and secretory cell lineages, the intestinal epithelium mounts a robust and multifaceted response to this potent pathogen. These discoveries not only expand the fundamental understanding of gut immunity but also chart a promising course towards new immunomodulatory therapies that could save lives in cholera-endemic regions.

As the global burden of cholera persists amidst climate change and increasing antibiotic resistance, leveraging endogenous cytokine pathways like IL-22-mediated mucosal defense offers hope for sustainable interventions. Future studies will need to validate these findings in human tissues and evaluate the safety and efficacy of IL-22Fc–based therapies in clinical settings. Nonetheless, this work sets a new benchmark for integrating single-cell transcriptional profiling with immunological insight to unravel complex host–pathogen interactions in the gut.

The research community and public health officials alike will closely watch how these revelations translate into practical measures to curb the impact of cholera and potentially other mucosal infections. The convergence of high-resolution single-cell methodologies, immunobiology, and therapeutic innovation heralds a new era in infectious disease control through smarter modulation of the body’s own defense systems.

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Subject of Research: Innate immune defenses in the small intestine protecting against Vibrio cholerae infection.

Article Title: IL-22 promotes genesis of small intestinal secretory cells that protect against cholera in mice.

Article References:
Suzuki, M., Hasegawa, Y., Zhang, H. et al. IL-22 promotes genesis of small intestinal secretory cells that protect against cholera in mice. Nat Microbiol (2026). https://doi.org/10.1038/s41564-026-02375-7

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41564-026-02375-7

Keywords: IL-22, Vibrio cholerae, cholera, small intestine, innate immunity, enterocyte specialization, goblet cells, mucus secretion, Reg3β, innate lymphoid cells, single-cell RNA sequencing, mucosal defense, cytokine therapy, intestinal colonization, diarrheal disease

A new batch of Pentagon videos and other records related to unidentified anomalous phenomena (UAP) is expected to soon be released by the Department of War, with many anticipating their arrival by week’s end.

The next installment in an ongoing series of Pentagon disclosures is anticipated to include up to 46 new UAP videos reportedly held by the Pentagon’s All-domain Anomaly Resolution Office (AARO).

Although the existence of the videos has been discussed publicly on several occasions by lawmakers in recent weeks, a complete listing of the collection of AARO UAP videos, along with preliminary titles and descriptions of some of the footage, was initially disclosed earlier this year in a letter from Representative Anna Paulina Luna (R-Fla.) to U.S. Secretary of War Pete Hegseth.

“The continued lack of transparency surrounding these anomalies and the potential national security threat they pose is troubling,” Luna’s letter, dated March 31, 2026, reads.

According to Luna, the existence of “additional video records of potential UAP sightings” came to the attention of Luna’s Task Force as a result of whistleblowers who participated in a September 29, 2025, hearing related to UAP transparency. “To continue its investigation, the Task Force requests certain video files related to UAP sightings,” Luna explained to Hegseth in the letter.

Indications of a Forthcoming Release?

The imminent arrival of the videos, originally requested for release by Luna “as soon as possible but no later than April 14, 2026,” is now anticipated by as early as Friday.

On Thursday, the official page on the Department of War’s website for the Presidential Unsealing and Reporting System for UAP Encounters (PURSUE) featured no additional videos or documents beyond those included with the original release, which appeared on May 8, 2026, when the page went live.

However, the heading originally titled “Release 01” that appears in the page’s navigation bar is now missing the “01,” seemingly indicating that preparations for a new batch, tentatively titled “Release 02,” are likely underway.

Update: Thursday, May 21, 2026: Some visitors to the Department of War website also reported throughout the day that, for a short period, the site’s file listing showed up to 140 blank pages. As of 7:23 p.m. Eastern, only the original number of files associated with “Release 01” is available on the site.

What To Expect in the PURSUE “Release 02”

Based on the original list of videos detailed in Luna’s letter from March, along with some descriptions and imagery associated with the videos that have been disseminated prior to their complete authorized release, a few details about what the videos are expected to reveal can be discerned.

One video that Luna and her Task Force have requested reportedly depicts a formation of four unidentified objects flying over an unspecified region in Iran, observed on August 26, 2022.

Another video, reportedly captured in 2021 over Syria, appears to show an object that seemingly displays “instant acceleration,” a capability that would require overcoming several fundamental laws of physics.

While unusual—or even seemingly impossible—physical maneuvers can often be attributed to camera motion and other artifacts arising from the conditions under which such videos are obtained, there are indications that there could be other intriguing footage in the forthcoming batch, a few of which may display a key capability that has increasingly been attributed to some UAP during military observations.

Unidentified Submerged Objects and “Transmedium” UAP

According to AARO, UAP sometimes represent more than just aerial phenomena, with its official definition including “sources of anomalous detections in one or more domains (i.e., airborne, seaborne, spaceborne, and/or transmedium) that are not yet attributable to known actors and that demonstrate behaviors that are not readily understood by sensors or observers.”

Intriguingly, at least some of the files expected in the forthcoming release include videos that purportedly show objects exhibiting what the military characterizes as “transmedium” capabilities, with the objects, described as “USOs” (unidentified submerged objects), reportedly observed both in and out of water.

In at least one of the two USO videos, several spherical objects observed in near proximity to a U.S. submarine on March 25, 2022, are reportedly observed both “in and out of water” in the AARO footage.

Another video, dubbed “UAP USO formation Wiley 2X Zinc,” reportedly shows a different formation of unidentified objects that may be displaying transmedium capabilities.

Spheres Take Center Stage

Several of the videos requested by Luna and other lawmakers reportedly feature what appear to be spherical objects, a common shape class that has been frequently reported by military personnel in recent years, as well as historical reports involving aerial phenomena.

One video, obtained on November 23, 2020, appears to show a spherical object operating in airspace over Afghanistan as it moves “in and out of clouds.” Another spherical object, filmed in 2022, reportedly displays “erratic movement” frequently attributed to such objects, while in a separate video, a spherical UAP is said to have been observed “pulsing” as it passed over a body of water.

Finally, in an incident that occurred on April 12, 2021, a series of three videos was obtained by U.S. personnel depicting a spherical object of unknown origin.

AARO officials have previously expressed interest in this class of objects. In one incident in 2022, an MQ-9 Reaper UAS operating in the Middle East recorded video of a spherical object using its onboard electro-optical sensor. “The object’s characteristics and behavior are consistent with other ‘metallic orb’ observations in the region,” according to a short summary of the footage included in a 2025 AARO mission brief available at its website.

Tic Tacs, Flying Cigars, “Fast Movers”

Spherical objects aren’t the only objects that make appearances in the videos AARO has obtained. Several other varieties of UAP that are commonly recognized from historical accounts are reportedly featured in the videos, which include elongated “cigar” shapes such as the “Tic Tac,” a designation first attributed to an unusual object captured by an FA/18 Super Hornet Pilot during training exercises off the Baja California Coast in November 2004.

One of the new videos describes a “cigar-shaped or fat spherical UAP” observed on October 15, 2022, while another appears to describe a case in which a United States Coast Guard EADS HC-144 Ocean Sentry aircraft observed a Tic Tac-shaped object with its high-definition forward-looking infrared (FLIR) sensor system.

Another video that could be in the forthcoming release involves a trio of “fast moving UAPs” that were observed by U.S. personnel on October 29, 2020. The term “fast mover” is recognized as slang for “fighter jet,” while similar terminology, such as the variant “Fastwalker,” is also occasionally used in relation to UAP sightings.

New Details on the Eglin Air Force Base UAP?

Some of the videos expected in the forthcoming release may offer additional details about UAP incidents that are already well known and for which case resolutions have been produced during AARO’s investigations.

One video in the forthcoming tranche, designated “IIR 1 665 SO301 23/Eglin AFB,” appears to refer to a January 26, 2023, incident involving a U.S. military pilot who observed four objects flying in a diamond formation over the Gulf of Mexico. At the time of the sighting, the pilot claimed that several of his aircraft’s onboard capabilities malfunctioned, requiring them to manually capture imagery of the object.

In a case resolution report on the incident following AARO’s assessment, investigators concluded that the UAP “very likely was an ordinary object and was not exhibiting anomalous or exceptional characteristics or flight behaviors,” concluding that the object the pilot filmed may have been a lighting balloon.

However, AARO’s resolution report added that it had only “moderate confidence in this assessment due to the limited data provided,” a conclusion that drew criticism from even some of the more skeptical UAP investigators.

“The lighting balloon hypothesis always felt like something someone at AARO liked, but wasn’t really supported by much evidence,” skeptic Mick West told The Debrief following the publication of AARO’s report on the incident.

Another of the videos in the forthcoming release was captured by a U.S. Air Force F-16C pilot (callsign AESIR11) during a widely publicized incident that occurred on February 12, 2023, where an object was shot down over Lake Huron with an AIM-9X Sidewinder missile.

According to former AARO director Sean Kirkpatrick, this incident had been one of several involving objects that were later determined to have been hobbyist balloons that were shot down in early 2023, as Kirkpatrick revealed during a recent presentation he gave at the Center for Naval Analyses on April 27, 2026.

Looking Ahead: Cooperation with AARO Continues

Luna has also conveyed to her followers on social media in recent days that the review process required for the release of the new videos was underway, with cooperation from AARO officials.

In a posting on her official X account on May 15, 2026, Luna appeared in a photograph alongside current AARO director Jon Kosloski and Rep. Eric Burlison (R-Mo.), writing that they had just completed the review of “40+ videos set for declassification” by the Department of War, which could be expected “in the coming weeks” as of the time of posting.

“We are standing with the NEW and very QUALIFIED Director of AARO who now has my full support and has proven through action that he is working in good faith on declass efforts,” Luna wrote.

It remains to be seen whether all the videos Luna has requested will be released, although a few glimpses of footage allegedly from the forthcoming batch have already appeared on social media in recent days.

Should the requested tranche of AARO UAP videos arrive in time for the unofficial, but widely anticipated deadline, The Debrief will provide additional reporting on the release of those records, along with any new information they may contain.

For the time being, the records released under the PURSUE initiative are available on the Department of War’s website.

Micah Hanks is the Editor-in-Chief and Co-Founder of The Debrief. A longtime reporter on science, defense, and technology with a focus on space and astronomy, he can be reached at micah@thedebrief.org. Follow him on X @MicahHanks, and at micahhanks.com.

An innovative new Japanese combat drone was recently unveiled by the country’s defense minister, who said the unmanned aerial systems are already being deployed in support of the country’s air defense capabilities.

The fixed-wing aircraft, developed by the Japanese defense company AirKamuy and appropriately named the AirKamuy 150, has been billed as a low-cost, environmentally friendly aerial system that can be produced quickly from readily available materials.

However, unlike most modern unmanned aerial systems developed for combat situations, the AirKamuy 150 is constructed almost entirely from something most wouldn’t expect: cardboard.

“Today, I had the opportunity to exchange opinions with everyone from Air Kamuy, which is renowned for its cardboard drones,” Japanese Defense Minister Shinjiro Koizumi said in a recent posting that appeared on his official X account.

“The Japan Maritime Self-Defense Force is already utilizing them as targets,” Koizumi said.

Last month, it was announced that Japan would be moving to institutionalize its drone warfare capabilities, with the launch of a new initiative involving the country’s Ground Self-Defense Force (GSDF).

The move highlights a notable shift in Japan’s preparations for future combat, particularly amid heightened tensions in the Pacific region. Japanese officials have also cited a “shrinking workforce” as another primary factor behind the recent ramp-up in drone capabilities.

On April 13, an official ceremony was held in Tokyo to recognize the launch of a pair of new offices that will manage the country’s drone production: the “Unmanned Defense Capability Promotion Office” and the “Unmanned Systems Office,” both launched on April 8.

“Taking into account the geographical characteristics of our nation as a maritime nation, we must realize new ways of fighting at the earliest possible time,” Shinjiro said during the April ceremony.

Shinjiro also said he aspires to see Japan’s Self Defense Forces become “the organization that makes the greatest use of unmanned assets in the world.”

In a December 2022 document detailing Japan’s National Defense Strategy, defense officials noted specifically that in the event of an invasion, “Japan would need to ensure asymmetric advantage by leveraging, in addition to these capabilities, manned as well as unmanned assets and gain superiority across domains such as underwater, surface, and air.”

The document further outlined the country’s objectives to strengthen its unmanned defense capabilities, as well as “crossdomain operation capabilities” and “command and control/intelligence-related functions.”

“Unmanned assets are often relatively affordable compared to manned equipment and have the great advantage of being able to minimize human loss and operate continuously for a long period of time,” the strategic document stated, noting that combining such capabilities with emerging technologies that include artificial intelligence could be “a game-changer that fundamentally transform force structure and way of warfare, enabling Japan to gain asymmetrical advantages in the air, sea, and underwater domains.”

“For this reason, these unmanned assets will be effectively utilized not only for information gathering and surveillance, but also for a wide range of missions including combat support,” the document states.

Defense Minister Koizumi said in his recent posting on X that his meeting with AirKamuy representatives produced “an extremely in-depth discussion,” adding that he hopes the collaboration will help Japan reach its goals for transforming and optimizing its air defense capabilities in the months ahead.

“In aiming to become the Self-Defense Forces that makes the most extensive use of unmanned assets, including drones, in the world, strengthening collaboration with startups enthusiastic about the defense sector is indispensable,” Koizumi said.

Micah Hanks is the Editor-in-Chief and Co-Founder of The Debrief. A longtime reporter on science, defense, and technology with a focus on space and astronomy, he can be reached at micah@thedebrief.org. Follow him on X @MicahHanks, and at micahhanks.com.

An analysis of six years of procurement records suggests that the People’s Liberation Army has openly tried to acquire restricted U.S. technology.

The low-orbit satellite constellation is intended to track aircraft, cruise missiles and other airborne threats

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